PFAS

per- and polyfluoroalkyl substances (“Forever Chemicals”)


Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical Mixture Using In Vitro Tests - November 29, 2025

J Appl Toxicol. 2025 Nov 29. doi: 10.1002/jat.70011. Online ahead of print.

ABSTRACT

Humans are chronically exposed to mixtures of environmental contaminants. Exposure to endocrine-disrupting chemicals (EDCs) contributes to increased health impairment observed globally. This study aimed to evaluate the endocrine-disruptive and oxidative stress potential of a human-relevant, complex chemical mixture in vitro. By testing chemical class subgroup mixtures, the identity of toxicological drivers and mixture additivity could be investigated. A 50-component mixture was compiled based on Swedish human blood concentrations (xHBC), consisting of six subgroup mixtures: polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (PCB mixture), brominated flame retardants (BFR mixture), per- and polyfluoroalkyl substances (PFAS mixture), pesticide mixture, synthetic phenolic contaminants (phenol mixture), and phthalate mixture. These were tested in four chemically activated luciferase gene expression (CALUX) assays: dioxin responsive (DR-), estrogen receptor α (ERα-), androgen receptor. (AR-), and nuclear factor erythroid 2-related factor 2 (Nrf2)-CALUX, along with an adipocyte cell assay. The total mixture caused significant agonistic activity in DR- and ER-, and antagonistic activity in AR-CALUX at 0.1-15 xHBC, depending on the assay. Mixture additivity was assessed in ERα-, DR-, and anti-AR-CALUX using subgroup mixtures and the concentration addition (CA) model. The total mixture followed the CA model in ERα-, anti-AR- and DR-CALUX. The toxicological drivers of these activities were mainly the PCB and phenol mixture. A significant increase in differentiated adipocytes was observed at 100 xHBC. These results raise concerns regarding potential health effects on the endocrine system. The additive effects at human-relevant concentrations observed in this study motivate considering mixtures in regulatory contexts to protect the well-being of future generations.

PMID:41317044 | DOI:10.1002/jat.70011


Evaluating the Endocrine-Disrupting and Oxidative Stress Potential of a 50-Component Human-Relevant Complex Chemical Mixture Using In Vitro Tests - November 29, 2025

J Appl Toxicol. 2025 Nov 29. doi: 10.1002/jat.70011. Online ahead of print.

ABSTRACT

Humans are chronically exposed to mixtures of environmental contaminants. Exposure to endocrine-disrupting chemicals (EDCs) contributes to increased health impairment observed globally. This study aimed to evaluate the endocrine-disruptive and oxidative stress potential of a human-relevant, complex chemical mixture in vitro. By testing chemical class subgroup mixtures, the identity of toxicological drivers and mixture additivity could be investigated. A 50-component mixture was compiled based on Swedish human blood concentrations (xHBC), consisting of six subgroup mixtures: polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (PCB mixture), brominated flame retardants (BFR mixture), per- and polyfluoroalkyl substances (PFAS mixture), pesticide mixture, synthetic phenolic contaminants (phenol mixture), and phthalate mixture. These were tested in four chemically activated luciferase gene expression (CALUX) assays: dioxin responsive (DR-), estrogen receptor α (ERα-), androgen receptor. (AR-), and nuclear factor erythroid 2-related factor 2 (Nrf2)-CALUX, along with an adipocyte cell assay. The total mixture caused significant agonistic activity in DR- and ER-, and antagonistic activity in AR-CALUX at 0.1-15 xHBC, depending on the assay. Mixture additivity was assessed in ERα-, DR-, and anti-AR-CALUX using subgroup mixtures and the concentration addition (CA) model. The total mixture followed the CA model in ERα-, anti-AR- and DR-CALUX. The toxicological drivers of these activities were mainly the PCB and phenol mixture. A significant increase in differentiated adipocytes was observed at 100 xHBC. These results raise concerns regarding potential health effects on the endocrine system. The additive effects at human-relevant concentrations observed in this study motivate considering mixtures in regulatory contexts to protect the well-being of future generations.

PMID:41317044 | DOI:10.1002/jat.70011


Sex-specific association of prenatal exposure to halogenated persistent organic pollutants (Hal-POPs) with neonatal sex hormone levels and birth size: a birth cohort study using meconium as a biomonitoring matrix - November 29, 2025

Environ Int. 2025 Nov 22;206:109953. doi: 10.1016/j.envint.2025.109953. Online ahead of print.

ABSTRACT

Halogenated persistent organic pollutants (Hal-POPs) are endocrine disruptors that posing risks to fetal development via transplacental transfer. This study utilized neonatal meconium, a non-invasive matrix reflecting cumulative exposure during the second- and third-trimester, to assess prenatal levels of per- and polyfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs) in 271 mother-infant pairs from Guangzhou, China. The associations between Hal-POP exposure, neonatal sex hormones, and birth size Z-scores [weight (BWZ), length (BLZ), head circumference (HCZ)], as well as the potential hormonal mediation were explored. Results showed ubiquitous Hal-POP detection, with 4:2 fluorotelomer sulfonic acid (4:2 FTSA; median: 0.53 nmol/g), BDE-47 (0.11 nmol/g), and p, p'-DDE (0.04 nmol/g) being the dominant chemicals within their respective classes. 4:2 FTSA levels were higher in male neonates (p < 0.05). Generalized linear models (GLMs) revealed sex-specific endocrine association of 4:2 FTSA, elevating androgens [testosterone (T) and dihydrotestosterone (DHT)] and reducing estrogens [estrone (E1) and estriol (E3)] and progesterone (P4) in males, whereas only decreasing E1 modestly in females. Bayesian Kernel Machine Regression (BKMR) identified PFASs (Group-PIP ≥ 0.98) as the primary contributors to elevated androgen (T and DHT) and reduced E3, with 4:2 FTSA as the key driver (Cond-PIP ≥ 0.95). Mediation analyses revealed that both E1 and E3 mediated 22.2 % of the negative association between 4:2 FTSA and BLZ. Sex-stratified analyses showed E3 mediated 22.8 % of this relationship in males, while exerted a suppression effect on the 4:2 FTSA-HCZ associations in females. Molecular docking revealed that 4:2 FTSA exhibits high-affinity binding to key steroidogenic enzymes (including CYP19A1, 17β-HSD1, AKR1C2, and AKR1C3), suggesting direct disruption on steroid hormone synthesis. This study highlights the endocrine-disrupting potential of emerging PFAS alternatives and their sex-specific effects on fetal growth, providing critical evidence for targeted strategies to reduce prenatal Hal-POP exposure and associated developmental risks.

PMID:41317605 | DOI:10.1016/j.envint.2025.109953


Sex-specific association of prenatal exposure to halogenated persistent organic pollutants (Hal-POPs) with neonatal sex hormone levels and birth size: a birth cohort study using meconium as a biomonitoring matrix - November 29, 2025

Environ Int. 2025 Nov 22;206:109953. doi: 10.1016/j.envint.2025.109953. Online ahead of print.

ABSTRACT

Halogenated persistent organic pollutants (Hal-POPs) are endocrine disruptors that posing risks to fetal development via transplacental transfer. This study utilized neonatal meconium, a non-invasive matrix reflecting cumulative exposure during the second- and third-trimester, to assess prenatal levels of per- and polyfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs) in 271 mother-infant pairs from Guangzhou, China. The associations between Hal-POP exposure, neonatal sex hormones, and birth size Z-scores [weight (BWZ), length (BLZ), head circumference (HCZ)], as well as the potential hormonal mediation were explored. Results showed ubiquitous Hal-POP detection, with 4:2 fluorotelomer sulfonic acid (4:2 FTSA; median: 0.53 nmol/g), BDE-47 (0.11 nmol/g), and p, p'-DDE (0.04 nmol/g) being the dominant chemicals within their respective classes. 4:2 FTSA levels were higher in male neonates (p < 0.05). Generalized linear models (GLMs) revealed sex-specific endocrine association of 4:2 FTSA, elevating androgens [testosterone (T) and dihydrotestosterone (DHT)] and reducing estrogens [estrone (E1) and estriol (E3)] and progesterone (P4) in males, whereas only decreasing E1 modestly in females. Bayesian Kernel Machine Regression (BKMR) identified PFASs (Group-PIP ≥ 0.98) as the primary contributors to elevated androgen (T and DHT) and reduced E3, with 4:2 FTSA as the key driver (Cond-PIP ≥ 0.95). Mediation analyses revealed that both E1 and E3 mediated 22.2 % of the negative association between 4:2 FTSA and BLZ. Sex-stratified analyses showed E3 mediated 22.8 % of this relationship in males, while exerted a suppression effect on the 4:2 FTSA-HCZ associations in females. Molecular docking revealed that 4:2 FTSA exhibits high-affinity binding to key steroidogenic enzymes (including CYP19A1, 17β-HSD1, AKR1C2, and AKR1C3), suggesting direct disruption on steroid hormone synthesis. This study highlights the endocrine-disrupting potential of emerging PFAS alternatives and their sex-specific effects on fetal growth, providing critical evidence for targeted strategies to reduce prenatal Hal-POP exposure and associated developmental risks.

PMID:41317605 | DOI:10.1016/j.envint.2025.109953


Nationwide occurrence and flux estimates of PFAS in leachate from waste-to-energy sector: an emerging reservoir linked to short-term waste storage - November 29, 2025

Water Res. 2025 Nov 25;290:125045. doi: 10.1016/j.watres.2025.125045. Online ahead of print.

ABSTRACT

Although leachates from post-consumer waste disposal are increasingly recognized as significant reservoirs of per- and polyfluoroalkyl substances (PFAS), the leachate generated during short-term waste storage in the Waste-to-Energy sector remains underexplored, limiting comprehensive understanding of PFAS release pathways in modern waste management. This study investigated PFAS in raw leachate and after on-site treatment from 48 municipal solid waste incineration (MSWI) facilities, revealing national occurrence patterns, key drivers, and mass fluxes from this emerging release pathway. Mass transfer-driven leaching of highly soluble short-chain PFAS during waste storage prior to incineration led to ∑PFAS concentrations of 10.7-47.8 μg/L, with intra-facility variability shaped by both leaching-relevant and socio-economic factors. Longer storage duration increased total PFAS and long-chain fractions, while greater leachate yields enhanced overall mass transfer. Regionally, PFAS profiles reflected class-specific socio-economic influences: short-chain PFCAs, primarily from consumer waste, exhibited regional patterns associated with administrative hierarchy and economic conditions, whereas industrial fluorochemical sources were likely related to elevated PFBS, PFHxS, PFOA, and HFPO-DA levels, with PFBS and HFPO-DA showing persistence post-treatment. Monte Carlo simulations estimated an average PFAS flux of 1180 kg/y in raw leachate, exceeding the estimated national landfill leachate flux (419 kg/y), while that in treated effluent was 8.74 kg/y. These results demonstrate that PFAS in MSWI leachate represent a substantial and previously overlooked source that is particularly enriched in short-chain and industry-linked alternatives, providing a comprehensive dataset to inform risk assessment and guide targeted control strategies.

PMID:41317627 | DOI:10.1016/j.watres.2025.125045


Acute toxicity, behaviour, metabolism, and transcriptomic points of departure in embryo-larval zebrafish exposed to nine different PFAS - November 28, 2025

J Hazard Mater. 2025 Nov 24;500:140599. doi: 10.1016/j.jhazmat.2025.140599. Online ahead of print.

ABSTRACT

Most per- and poly-fluoroalkyl substances (PFAS) lack toxicity data, and the hazards associated with different PFAS chemical structures have not been systematically assessed using in vivo models. To address this gap, we compared the toxicity of nine PFAS in embryo-larval zebrafish, an emerging alternative to conventional in vivo models. Exposures were conducted from 0 to 5 days post-fertilization with semi-static renewal. We then evaluated three apical toxicity endpoints (developmental toxicity (mortality/malformation), swimming behaviour, and metabolic activity) alongside gene expression changes using high-throughput transcriptomics. These data were used to derive apical and transcriptomic points of departure (aPODs and tPODs, respectively). Transcriptomic benchmark concentration modeling in BMDExpress v3.2 was performed to derive tPODs using multiple approaches. Overall, PFAS potency increased with longer fluorinated carbon chain lengths and was greater for PFAS containing sulfonic groups. tPODs were generally the most sensitive endpoints, typically falling within a 10-fold range below aPODs. Our results support previous findings that tPODs provide suitably conservative PODs for chemical toxicity assessment. Our results contribute new data on PFAS early-life stage toxicity and demonstrate an economical and ethically viable high-throughput platform for systematic evaluation of chemical hazards and potencies for risk assessment applications.

PMID:41313855 | DOI:10.1016/j.jhazmat.2025.140599


Prenatal exposure to PFAS, associations with child cognitive ability and modification by maternal Vitamin D status: The MABC study - November 28, 2025

J Hazard Mater. 2025 Nov 24;500:140595. doi: 10.1016/j.jhazmat.2025.140595. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal per- and polyfluoroalkyl substances (PFAS) exposure may adversely influence neurodevelopment. However, few studies have considered whether cumulative PFAS exposure over the entire course of pregnancy impacts child cognitive development and whether nutritional factors modify these associations.

OBJECTIVES: To investigate whether Vitamin D status modifies the association between maternal PFAS exposure during pregnancy and child cognitive ability.

METHODS: This analysis used 728 mother-child pairs in the Ma'anshan Birth Cohort (MABC), a population-based Chinese birth cohort enrolled from 2013 to 2014. We measured and averaged serum PFAS and Vitamin D concentrations during the first, second, and third trimesters of pregnancy. Child cognitive ability was assessed at age 2.7-6.0 years using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition. We used linear regression, Bayesian kernel machine regression, and quantile g-computation to estimate covariate-adjusted associations of individual PFAS concentrations and their mixture with child cognitive scores. Analyses were stratified by sex to examine sex-specific associations between PFAS and child cognitive scores, with further stratification by categorizing maternal Vitamin D levels into deficient (<20 ng/mL, n = 636) and non-deficient (≥ 20 ng/mL, n = 92) groups.

RESULTS: Overall, the pregnancy average of br-PFOA concentrations was inversely associated with VCI scores (β = -1.72, 95 %CI: -3.43, -0.02), 8:2 Cl-PFESA was inversely associated with VSI scores (β = -1.21, 95 %CI: -2.30, -0.11), and n-PFHxS was inversely associated with WMI scores (β = -2.19, 95 %CI: -4.35, -0.03). Generally, PFAS were associated with lower cognitive scores in boys, but not girls. Further, the PFAS mixture was negatively associated with boys' total cognitive scores (β = -1.94, 95 %CI: -3.69, -0.19), with br-PFOA and n-PFHxS having the greatest weights; in contrast, PFHpS was the major contributor to the positive association of the PFAS mixture with cognitive scores in girls. After stratifying by maternal Vitamin D status, adverse associations were primarily observed in the deficient group among boys, whereas positive associations were present only in the deficient group among girls. Specifically, associations of cognitive scores with n-PFOA, br-PFOA, PFNA, n-PFHxS, and br-PFHxS were significantly stronger among boys born to women with Vitamin D deficiency (Range of betas=-4.73 to -2.04, P < 0.05) than those with sufficient levels of Vitamin D (Range of betas=-3.81-1.52, P > 0.05). The PFAS mixture was negatively related to child cognitive ability in boys, where each quartile increase in the mixture was associated with boys' VCI, VSI, WMI, and FSIQ scores decreased by 2.77, 2.21, 2.57, and 1.94 scores, respectively (all p-FDR < 0.05).

CONCLUSION: We observed sex-specific adverse associations between prenatal PFAS and cognitive ability. Our findings suggest that prenatal Vitamin D may modify these associations, potentially mitigating the neurotoxic effects of prenatal PFAS exposure.

PMID:41313860 | DOI:10.1016/j.jhazmat.2025.140595


Microplastics and PFAS as ubiquitous pollutants affect potencies of highly toxic chemicals in mixtures - November 28, 2025

J Hazard Mater. 2025 Nov 21;500:140493. doi: 10.1016/j.jhazmat.2025.140493. Online ahead of print.

ABSTRACT

Pollutants usually occur as mixtures in the environment, where they affect each other's toxicity even at non-toxic concentrations. Despite the environmental relevance of interactions in complex mixtures, they remain severely understudied. Therefore, this study aimed to assess how PFAS and microplastics (MPs) as ubiquitous pollutants at (non-)toxic concentrations affect the potencies of highly toxic chemicals in mixtures. Experiments were performed to assess the toxicity of perfluorobutane sulfonamide (FBSA), linear low-density polyethylene MPs (0-50 µm), chlorpyrifos and imidacloprid to the reproduction of the springtail Folsomia candida in Lufa 2.2 soil, as single compounds, binary and ternary mixtures. FBSA at non-toxic concentrations showed dose-dependent synergism with imidacloprid, but antagonism with chlorpyrifos. Synergism only occurred in the ternary mixtures dominated by FBSA at non-toxic concentrations and imidacloprid. MPs and toxic concentrations of FBSA were antagonistic in all mixtures. In conclusion, MPs and FBSA affected insecticide toxicity, and assuming concentration addition for the hazard assessment of ternary mixtures is generally precautionary. Ternary interactions could not be reliably predicted from binary interactions, and ratio-specific interactions may be overlooked. This emphasizes the need to include experimental mixture toxicity data for a realistic risk assessment of complex chemical mixtures.

PMID:41313859 | DOI:10.1016/j.jhazmat.2025.140493


High-throughput prediction of PFAS binding affinities with human liver-fatty acid binding protein using machine learning and QSAR model - November 28, 2025

Environ Int. 2025 Nov 24;206:109960. doi: 10.1016/j.envint.2025.109960. Online ahead of print.

ABSTRACT

The binding affinity with human liver-fatty acid binding protein (Kd FABP) is a key parameter to characterize the accumulation potential of per- and polyfluoroalkyl substances (PFAS) in animal liver. However, the vast number of PFAS, combined with the limited available commercial standards, makes it a major challenge to measure their Kd FABP. In this study, the Kd FABP of 44 PFAS standards, and 72 PFAS extracted and semi-quantified in environmental samples by suspect screening analysis were measured using ultrafiltration methods. Several machine learning regression algorithms were developed to predict the Kd FABP, and extreme gradient boosting regression exhibited the best performance. Of note, intrinsic molecular descriptors, such as AATS0d, AATS8pe, VR1_A, ATSC1d, and AATSC2Z were found to be the primary factors to affect the binding affinities. The optimized model was then applied to predict the Kd FABP values of 9117 PFAS listed by U.S. EPA. DTXSID40896722, which features perfluorinated branches connected through sulfonyl linkages, exhibits the lowest Kd FABP value. Additionally, by combining the predicted Kd FABP of 76,216 artificial-intelligence-generated PFAS, it was found that chemical fragments containing carbon-fluorine and ether moieties are conducive for the binding. This study holds significant importance in de novo design of environmentally friendly PFAS.

PMID:41314140 | DOI:10.1016/j.envint.2025.109960


Differential impact of per- and polyfluoroalkyl substances exposure on hypertension risk by kidney function and metabolic status - November 28, 2025

Environ Int. 2025 Nov 25;206:109930. doi: 10.1016/j.envint.2025.109930. Online ahead of print.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants increasingly linked to hypertension. However, the modifying effects of kidney function and metabolic health remain unclear. This study examined the associations between serum PFAS concentrations and hypertension, with a particular focus on kidney function and metabolic status as potential effect modifiers.

METHODS: Data were obtained from the Korean National Environmental Health Survey (KoNEHS, 2018-2020), which included adults aged 19 years or older with available serum PFAS, blood pressure, and kidney function data. Adjusted odds ratios for hypertension were estimated using multivariable logistic regression across PFAS quartiles, with stratified analyses by kidney function and metabolic status.

RESULTS: Among 2,993 participants, elevated levels of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and total PFAS were associated with higher hypertension risk. Associations were more evident in individuals in the higher eGFR group, whereas effect estimates were attenuated in those with lower eGFR. In quartile-based analyses, positive exposure-response trends were observed for most PFAS, supporting the consistency of associations across exposure levels. Associations were stronger in participants with favorable metabolic profiles (e.g., without central obesity, normal triglycerides, high high-density lipoprotein cholesterol, normoglycemia) but attenuated in those with metabolic abnormalities.

CONCLUSIONS: PFAS exposure is associated with an increased risk of hypertension, particularly among those in the higher eGFR range and favorable metabolic profiles. These findings highlight the need to consider related disease phenotypes when assessing PFAS-associated cardiovascular toxicity and emphasize the importance of exposure mitigation in the healthy general population.

PMID:41314137 | DOI:10.1016/j.envint.2025.109930


Structure-related differences in plasma protein binding of per- and polyfluoroalkyl substances in mice and humans - November 28, 2025

Environ Toxicol Pharmacol. 2025 Nov 26:104879. doi: 10.1016/j.etap.2025.104879. Online ahead of print.

ABSTRACT

Understanding interspecies and structure-based differences in the toxicokinetics of perfluoroalkyl substances (PFAS) is important to explain their persistence and improve health risk assessment. Since renal clearance is the main elimination pathway, this study measured the free (protein-unbound) fraction (fu) of PFAS in human and mouse plasma using the DianormR system, selected for its robustness and rapid equilibrium. Sixteen PFAS were tested, including perfluoroalkyl carboxylic acids (PFCA), sulfonic acids (PFSA), and ether derivatives (PFECA). Mean fu values ranged from 0.21% (PFOS) to 50% (PFPeA) in mice and from 0.02% (PFHpS) to 8.5% (PFPeA) in humans. Interspecies differences were most pronounced for short-chain PFAS and PFECA, but not observed for longer chains. A U-shaped relationship between fu and molecular weight (MW) was found, with the lowest values near 400-500g/mol. These results highlight plasma protein binding as a key determinant of PFAS persistence and provide predictive models linking fu to MW.

PMID:41314320 | DOI:10.1016/j.etap.2025.104879


Per- and Polyfluoroalkyl Substances induce cytotoxicity in NCI-H446 cells through modulating proliferation, apoptosis, and m<sup>6</sup>A methylation - November 28, 2025

Food Chem Toxicol. 2025 Nov 26:115868. doi: 10.1016/j.fct.2025.115868. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS), a class of environmental pollutants with strong environmental persistence and bioaccumulation. However, the potential impacts and related mechanisms on small cell lung cancer (SCLC) remain unclear. This study integrated techniques including CCK8, qRT-PCR, and Flow Cytometry in NCI-H446 cells to compare the cytotoxicity of perfluorooctanoic acid (PFOA, a representative traditional PFAS) and its substitute Gen-X, and explore their associated mechanisms with cell proliferation, apoptosis, and m6A epigenetic regulation. Results showed both PFOA and Gen-X exerted significant toxicity on NCI-H446 cells, with Gen-X being less toxic than PFOA. Low-concentration PFOA (10 μM) significantly promoted cell proliferation, while Gen-X showed no such effect at the same concentration. At elevated exposure concentrations (100, 400 μM), both PFOA and Gen-X significantly inhibited cell proliferation and induced cell apoptosis. Additionally, they notably altered the expression of key regulators of cellular m6A methylation modification (e.g., WTAP, YTHDF1/3), with PFOA interfering more significantly with the m6A regulatory network than Gen-X. This study elucidates the distinct toxic effects of PFOA and its substitute Gen-X on SCLC cells, revealing their mechanisms through proliferation, apoptosis, and m6A regulation, thereby providing new insights into PFAS-related lung cancer risk and environmental health assessment.

PMID:41314428 | DOI:10.1016/j.fct.2025.115868


Pregnancy blood pressure trajectories in relation to high PFAS exposure: A longitudinal study from the Ronneby mother-child cohort - November 28, 2025

Environ Res. 2025 Nov 26:123431. doi: 10.1016/j.envres.2025.123431. Online ahead of print.

ABSTRACT

INTRODUCTION: Maternal blood pressure (BP) is crucial for the health of both mother and fetus, with long-term implications for the child's health. Studies exploring the link between perfluoroalkyl substances (PFAS) exposure and hypertensive disorders of pregnancy often yield inconsistent results, frequently focusing on a single BP measurement rather than longitudinal measurements. This study characterized the systolic and diastolic BP trajectories during pregnancy and determined their association with PFAS exposure in Ronneby, Sweden, where a third of the population was highly exposed from contaminated drinking water.

METHODS: We used longitudinal data from the Ronneby Mother-Child Cohort. Nine PFAS were measured in a serum sample collected during pregnancy and BP measurements were taken as part of the routine pregnancy monitoring program. BP trajectories were identified by Group Based Trajectory Modelling. Odds ratios (OR) for membership in each trajectory by PFAS quartiles were calculated via multinomial logistic regression models and Quantile G-computation was applied to quantify the joint effect of PFAS.

RESULTS: The study comprised 214 women with 1705 BP measurements. PFOS and PFHxS were detected at the highest concentrations (medians 16.6 and 10.2 ng/mL). Trajectory analysis identified a cubic shape three-trajectory solution, with one trajectory having elevated BP throughout pregnancy. Higher PFAS concentrations seemed to increase the probability of belonging to the high-BP trajectory in both single-pollutant and multi-pollutant models.

CONCLUSIONS: Higher PFAS exposure was associated with an increased OR of an adverse BP trajectory, underscoring the importance of monitoring pregnancy BP in communities with elevated PFAS exposures.

PMID:41314494 | DOI:10.1016/j.envres.2025.123431


Perfluorooctanoic acid and perfluorooctanesulfonic acid induce resistance to chemotherapy in colorectal cancer - November 28, 2025

J Hazard Mater. 2025 Nov 22;500:140583. doi: 10.1016/j.jhazmat.2025.140583. Online ahead of print.

ABSTRACT

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are non-volatile environmental pollutants that are ubiquitous in nature. Colorectal cancer (CRC) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. As one of the primary treatment modalities for CRC, chemotherapy often encounters drug resistance as its greatest obstacle to effective treatment. Exposure to PFAS has been shown to be associated with the progression of multiple tumors and the impact on treatment responses. However, their association with the efficacy of chemotherapy treatment for CRC remains unclear. This study aims to systematically investigate the effects of PFOA and PFOS on chemotherapy resistance in CRC and their underlying molecular mechanisms through in vitro and in vivo experiments. The results indicated that PFOA and PFOS significantly increased the resistance of HCT116 and SW620 cells to Oxaliplatin (OXA), 5-Fluorouracil (5-FU), and Irinotecan (CPT-11). Further studies revealed that PFOA and PFOS reverse the cell cycle arrest effect of chemotherapeutic drugs on CRC cells by regulating the expression of Cyclin A2 and CDK2. Exposure to PFAS may potentially elevate the risk of chemotherapy resistance in CRC, a finding that has significant implications for clinical treatment and chemical risk assessment.

PMID:41313853 | DOI:10.1016/j.jhazmat.2025.140583


Microplastics and PFAS as ubiquitous pollutants affect potencies of highly toxic chemicals in mixtures - November 28, 2025

J Hazard Mater. 2025 Nov 21;500:140493. doi: 10.1016/j.jhazmat.2025.140493. Online ahead of print.

ABSTRACT

Pollutants usually occur as mixtures in the environment, where they affect each other's toxicity even at non-toxic concentrations. Despite the environmental relevance of interactions in complex mixtures, they remain severely understudied. Therefore, this study aimed to assess how PFAS and microplastics (MPs) as ubiquitous pollutants at (non-)toxic concentrations affect the potencies of highly toxic chemicals in mixtures. Experiments were performed to assess the toxicity of perfluorobutane sulfonamide (FBSA), linear low-density polyethylene MPs (0-50 µm), chlorpyrifos and imidacloprid to the reproduction of the springtail Folsomia candida in Lufa 2.2 soil, as single compounds, binary and ternary mixtures. FBSA at non-toxic concentrations showed dose-dependent synergism with imidacloprid, but antagonism with chlorpyrifos. Synergism only occurred in the ternary mixtures dominated by FBSA at non-toxic concentrations and imidacloprid. MPs and toxic concentrations of FBSA were antagonistic in all mixtures. In conclusion, MPs and FBSA affected insecticide toxicity, and assuming concentration addition for the hazard assessment of ternary mixtures is generally precautionary. Ternary interactions could not be reliably predicted from binary interactions, and ratio-specific interactions may be overlooked. This emphasizes the need to include experimental mixture toxicity data for a realistic risk assessment of complex chemical mixtures.

PMID:41313859 | DOI:10.1016/j.jhazmat.2025.140493


Unravelling the magnitude and drivers of PFAS trophic magnification: a meta-analysis - November 28, 2025

Nat Commun. 2025 Nov 28;16(1):10720. doi: 10.1038/s41467-025-65746-4.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) threaten ecosystems worldwide due to their persistence, bioaccumulation, and toxicity. Through a global-scale meta-analysis of 119 aquatic and terrestrial food webs from 64 studies, we analyse 1009 trophic magnification factors (TMFs) for 72 PFAS and identify key variability drivers. On average, PFAS concentrations double with each trophic level increase (mean TMF = 2.00, 95% CI:1.64-2.45), though magnification varies considerably by compound. Notably, the industrial alternative F-53B exhibits the highest magnification (TMF = 3.07, 95% CI:2.41-3.92), a critical finding given its expanding use and minimal regulatory scrutiny. Methodological disparities across studies emerge as the dominant source of TMF variability. Our models explain 85% of the variation in TMFs, underscoring predictive capacity. This synthesis establishes PFAS as persistent trophic multipliers and provides a framework to prioritise high-risk compounds and harmonise biomagnification assessments. Our results call for consideration of stricter PFAS regulation to curb cascading ecological and health impacts.

PMID:41315316 | PMC:PMC12663151 | DOI:10.1038/s41467-025-65746-4


Arsenic, Cadmium, Lead, Mercury, and PFAS Exposure During Pregnancy or Lactation and Respective Concentrations in Human Milk: Systematic Review - November 28, 2025

Environ Res. 2025 Nov 26:123433. doi: 10.1016/j.envres.2025.123433. Online ahead of print.

ABSTRACT

Contaminant exposure during pregnancy or lactation may result in contaminant transfer into human milk (HM). This systematic review (PROSPERO# CRD42024530326) assessed relationships between arsenic, cadmium, lead, mercury, and per- and polyfluoroalkyl substances (PFAS) exposure measured by various biospecimen concentrations collected during pregnancy or lactation and respective concentrations in HM using studies conducted in countries rated 'high' or 'very high' on the Human Development Index. CAB Abstracts, CENTRAL, CINAHL, Embase, and MEDLINE, were searched for peer-reviewed English language articles through April 2, 2025. Direction, magnitude, and statistical significance of reported correlations (r, ρ, β, or unspecified) were synthesized narratively. Risk of bias (ROB) was assessed using ROBINS-E. Certainty of evidence was assessed using GRADE. From 3836 records identified, 48 articles from 46 studies (16 prospective cohorts, 30 cross-sectional) conducted in 25 countries were included (arsenic n=4 articles, cadmium n=5, lead n=18, mercury n=15, PFAS n=10). Higher exposure to lead, mercury, PFOA, and PFOS during pregnancy or lactation correlated with higher concentrations of these contaminants in HM, respectively (correlation=0.05-0.88 for lead, 0.0265-0.66 for mercury, 0.353-0.97 for PFOA, and 0.32-0.97 for PFOS). Certainty of evidence was moderate for lead, PFOA, and PFOS, and low for mercury. The evidence for arsenic and cadmium was limited and inconclusive, as well as evidence about these contaminants specifically from foods. In conclusion, higher exposure to lead, mercury, PFOA, and PFOS during pregnancy or lactation correlated with concentrations of these contaminants in HM. Reducing contaminant exposure during pregnancy or lactation could potentially reduce concentrations in HM.

PMID:41314500 | DOI:10.1016/j.envres.2025.123433


Biotransformation and partitioning of structurally different PFAS by wastewater microbial consortia - November 28, 2025

Environ Sci (Camb). 2025 Oct 27. doi: 10.1039/d5ew00528k. Online ahead of print.

ABSTRACT

Water resource recovery facilities (WRRFs) are sinks of legacy and replacement per- and polyfluoroalkyl substances (PFAS). This study evaluates the potential biotransformation, bioaccumulation, and adsorption of PFAS in wastewater sludge. Individual partitioning of parent PFAS and transformation products were measured in aqueous and solid phases of aerobic and anaerobic bacterial cultures for five structurally variable legacy and replacement PFAS using independent tests: perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorobutane sulfonic acid (PFBS), 6:2 fluorotelomer sulfonate (6:2 FTS), and hexafluoropropylene oxide dimer acid (GenX). Anaerobic cultures (anaerobic digestate and dehalogenating KB-1®) showed only adsorption (10.9-38.3%) with no transformation of the parent PFAS, irrespective of structural variances, in 90 days. Aerobic cultures from activated and nitrification sludge resulted in adsorption (26.9 ± 1.2-55.8 ± 1.4%), biotic accumulation (13.35-17.55%), and transformation (28.96-47.87%) of long-chain PFAS in 21 days. Notably, PFOA, PFOS, and 6:2 FTS were rapidly transformed 47.87 ± 1.6%, 28.96 ± 0.6%, and 43.1 ± 1.0%, respectively, after a shift occurred in microbial community structure under batch growth after 6 days, with the generation of shorter-chain compounds (carboxylates and sulfonates) and limited defluorination. Aerobic wastewater microbial communities converged, with Methylophilus, Acidomonas, Pseudomonas, Clostridium, Klebsiella, and Acinetobacter positively correlated with PFAS degradation. This study highlights the importance of unit processes and microbial community structure in controlling the fate and transport of select PFAS.

PMID:41312088 | PMC:PMC12652306 | DOI:10.1039/d5ew00528k


Wild turkeys off the menu in Maine after ‘forever chemicals’ found in birds - November 27, 2025

Contamination of wildlife with Pfas, which can increase risk of cancer, a growing problem in US

Hunters in Maine have been warned not to eat wild turkeys in parts of the state, after the birds were found to contain “forever chemicals” that can cause an increased risk of cancer.

Maine officials warned that high levels of Pfas – per- and polyfluoroalkyl substances – have been detected in wild turkey and deer killed and harvested in areas in the south-west of the state.

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Cumulative Exposure and Health Risk Assessment of PFAS in Animal-Derived Foods Using the Relative Potency Factor Approach - November 27, 2025

Toxics. 2025 Oct 30;13(11):931. doi: 10.3390/toxics13110931.

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are persistent and bioaccumulative contaminants frequently detected in animal-derived foods, raising concerns for consumer health. In 2020, the European Food Safety Authority (EFSA) established a group tolerable weekly intake (TWI) of 4.4 ng/kg bw per week for four PFAS (PFOA, PFNA, PFOS, PFHxS) based on immunotoxicity, prompting the European Commission to set maximum levels in food. However, many other PFAS are present in the diet, and their cumulative risk is poorly characterized. This study applied the Relative Potency Factor (RPF) approach, using hepatic toxicity as the reference endpoint. The RPF approach addresses a key challenge in assessing human dietary exposure to PFAS by enabling cumulative risk assessment for complex mixtures found in food, moving beyond single-compound evaluations. Occurrence data from EFSA's 2020 opinion were combined with European consumption data for fish, meat, eggs, and milk across four population groups (toddlers, adolescents, adults, elderly). Exposure estimates, expressed in PFOA equivalents, were compared with the group TWI. Results showed toddlers as the most vulnerable, with cumulative exposure approaching or exceeding TWI through fish, meat, and eggs, while milk contributed less. PFOS and PFOA were the main contributors across all food categories, with PFNA and PFDA also relevant, especially in younger populations. The findings highlight the added value of the RPF approach for cumulative PFAS risk assessment and emphasize the need for updated monitoring, refinement of potency factors for under-studied PFAS, and continued regulatory measures to protect high-risk consumers.

PMID:41304483 | PMC:PMC12656023 | DOI:10.3390/toxics13110931


A CpG Epigenetic Switch Reverts PFAS ToxicityAn In Vitro Study - November 27, 2025

Environ Health (Wash). 2025 Aug 21;3(11):1406-1422. doi: 10.1021/envhealth.5c00162. eCollection 2025 Nov 21.

ABSTRACT

Perfluorooctanesulfonic acid (PFOS) is a persistent environmental pollutant widely present in ecosystems and humans, linked to numerous diseases, including cancers, due to its potent toxicity. Despite its harmful effects, effective strategies for mitigating PFOS-induced toxicity remain undeveloped or at best underdeveloped. In this effort, we explore the concept of toxicity reversal by loci-specific DNA methylation editing to reverse PFOS-induced toxicity, whereby key cellular processes such as proliferation, migration, and apoptosis are restored. To demonstrate our concept, we employed CRISPR-dCas9 epigenome editing tools, utilizing catalytically deactivated Cas9 fused with either DNA methyltransferases or ten-eleven translocation (TET) dioxygenase effectors for loci-specific epigenome editing. Gene expression changes related to kidney disease, metabolism, and DNA methylation pathways were first noted. Through reduced representation bisulfite sequencing (RRBS), we demonstrated how PFOS exposure disrupts the epigenetic landscape, altering transcription factor binding sites linked to tumorigenesis, inflammation, and stress. By methylation editing of a single CpG site in implicated genes such as TARS2 and MAP2K5, we effectively reversed PFAS-induced toxicity and restored essential cell functions. Our success in precise single-CpG methylation editing of target genes effectively reverses toxicity, marking the first application of epigenome editing tools to counteract the toxic effects of a persistent environmental contaminant (PFAS). Our approach offers promising potential for toxicological screening and the identification of therapeutic targets to mitigate adverse effects triggered by environmental toxicants.

PMID:41306297 | PMC:PMC12645307 | DOI:10.1021/envhealth.5c00162


A Critical Review of PFAS Analysis, Occurrence, and Fate in Wastewater Treatment Plants - November 27, 2025

Environ Sci Technol. 2025 Nov 27. doi: 10.1021/acs.est.5c09949. Online ahead of print.

ABSTRACT

Wastewater treatment plants (WWTPs) receive per- and polyfluoroalkyl substances (PFAS)-containing waste streams including municipal sewage, industrial waste, landfill leachate, and firefighting wastewater. The widespread use of PFAS in commercial and industrial applications results in complex mixtures entering WWTPs. Given the centrality of WWTPs to the cycling of these harmful contaminants, comprehensive identification and quantification of PFAS in WWTPs is an essential research topic. Herein we review research on the distribution and fate of PFAS in WWTPs globally and synthesize data from 505 WWTPs in 39 screened studies conducted since 2020. We examine common sampling methods, analytical techniques, and PFAS targeting strategies. PFAS concentrations vary widely across matrices, with target PFAS ranging from 0.8 ng/L to 66.9 μg/L in influents, 0.5 ng/L to 107 μg/L in effluents, and 0.001 to 533.6 ng/g dry weight in sludge. While legacy compounds like PFOA and PFOS remain prevalent, short-chain PFAS now dominate. Across 259 WWTPs, no significant difference was found between influent and effluent target PFAS concentrations, and removal efficiencies were generally low or negative. Up to 86% of total organic fluorine in influents was attributed to untargeted precursors, underscoring the need for further research into PFAS transformation and fate during treatment.

PMID:41307504 | DOI:10.1021/acs.est.5c09949


Association between Endocrine Disruptors and Surgical Congenital Malformations: Systematic Review and Meta-Analysis - November 27, 2025

J Pediatr Surg. 2025 Nov 25:162829. doi: 10.1016/j.jpedsurg.2025.162829. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal exposure to endocrine disruptors (EDs) represents a growing public health concern due to its potential association with congenital malformations requiring pediatric surgical intervention. The ubiquity of these chemicals in modern environments and their ability to interfere with normal hormonal development during critical fetal windows raises significant concerns for pediatric surgeons. This systematic review was registered prospectively in PROSPERO (CRD420251158778).

METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, Embase, Web of Science, and gray literature from 2010-2025 for observational studies evaluating prenatal exposure to phthalates, bisphenols, perfluorinated compounds (PFAS), and organochlorines, with outcomes of surgical congenital malformations. Quality was assessed using the Newcastle-Ottawa Scale and GRADE methodology. Random-effects meta-analysis was performed using R software.

RESULTS: Of 4,121 studies identified, 66 met inclusion criteria (total population: 35,732). According to the Newcastle-Ottawa Scale, 42 studies (64%) had high quality (≥7 points), 18 (27%) moderate quality (5-6 points), and 6 (9%) low quality (<5 points). Significant associations were found between ED exposure and hypospadias (pooled OR: 2.21, 95% CI: 1.15-3.27; I2=65.4%, p=0.003), cryptorchidism (OR: 1.85, 95% CI: 1.02-3.36; I2=58.2%, p=0.041), and congenital heart disease (OR: 1.39, 95% CI: 1.09-1.76; I2=42.1%, p=0.008). DEHP and DBP phthalates showed the highest risks for urogenital malformations (OR: 3.12, 95% CI: 1.45-6.72). First trimester exposure demonstrated the strongest associations across malformation types. GRADE evidence was rated as moderate to high for urogenital and cardiac anomalies but low for gastrointestinal and neural defects.

CONCLUSIONS: Prenatal ED exposure is significantly associated with increased risk of surgical congenital malformations, particularly male urogenital and cardiac anomalies. These findings support implementing preventive strategies during pregnancy and justify stricter regulatory policies to protect fetal health and reduce the surgical burden in pediatric populations.

LEVEL OF EVIDENCE: II (Systematic Review and Meta-Analysis).

PMID:41308826 | DOI:10.1016/j.jpedsurg.2025.162829


Lab-scale insights into the environmental fate of emerging contaminants from airport runoff - November 27, 2025

J Contam Hydrol. 2025 Nov 22;276:104784. doi: 10.1016/j.jconhyd.2025.104784. Online ahead of print.

ABSTRACT

Contaminants of emerging concern (CECs) present in runoff pose risks to groundwater quality during their infiltration. Understanding the processes that control their attenuation is therefore essential for designing effective mitigation strategies. This research investigates the attenuation capacity of loess sediments overlaying a major Cretaceous chalky aquifer in Belgium, as part of a pre-feasibility study of soil aquifer treatment (SAT) system using airport runoff. In particular, the study aims to assess the natural ability of these sediments to filter and biologically degrade detected contaminants in airport runoff, thereby reducing their concentrations to levels compliant with water quality standards. Controlled batch experiments were thus conducted to analyze the sorption and biodegradability of key CECs, including PFAS, alkylphenols and benzotriazoles. The experiments were performed in triplicate using batch reactors filled with sediments and synthetic runoff. An abiotic control was included to distinguish between sorption and biodegradation. Results revealed distinct attenuation behaviours. Nonylphenol diethoxylate showed the highest removal, driven entirely by biodegradation with no contribution from sorption. Benzotriazole, tolyltriazole, PFOS, and 6:2 FTS showed moderate attenuation, primarily due to sorption for PFAS compounds. The remaining PFAS, - PFOA, PFHxA, and PFECHS - exhibited low attenuation, limited by sorption and no biodegradation. These findings confirm that loess sediments can reduce loads of certain CECs and also highlight the persistence of PFAS in water during infiltration. The results provide critical parameters for modeling CECs transport during SAT operations and support the safe management of airport runoff as a recharge source.

PMID:41308605 | DOI:10.1016/j.jconhyd.2025.104784


Association between Endocrine Disruptors and Surgical Congenital Malformations: Systematic Review and Meta-Analysis - November 27, 2025

J Pediatr Surg. 2025 Nov 25:162829. doi: 10.1016/j.jpedsurg.2025.162829. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal exposure to endocrine disruptors (EDs) represents a growing public health concern due to its potential association with congenital malformations requiring pediatric surgical intervention. The ubiquity of these chemicals in modern environments and their ability to interfere with normal hormonal development during critical fetal windows raises significant concerns for pediatric surgeons. This systematic review was registered prospectively in PROSPERO (CRD420251158778).

METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, Embase, Web of Science, and gray literature from 2010-2025 for observational studies evaluating prenatal exposure to phthalates, bisphenols, perfluorinated compounds (PFAS), and organochlorines, with outcomes of surgical congenital malformations. Quality was assessed using the Newcastle-Ottawa Scale and GRADE methodology. Random-effects meta-analysis was performed using R software.

RESULTS: Of 4,121 studies identified, 66 met inclusion criteria (total population: 35,732). According to the Newcastle-Ottawa Scale, 42 studies (64%) had high quality (≥7 points), 18 (27%) moderate quality (5-6 points), and 6 (9%) low quality (<5 points). Significant associations were found between ED exposure and hypospadias (pooled OR: 2.21, 95% CI: 1.15-3.27; I2=65.4%, p=0.003), cryptorchidism (OR: 1.85, 95% CI: 1.02-3.36; I2=58.2%, p=0.041), and congenital heart disease (OR: 1.39, 95% CI: 1.09-1.76; I2=42.1%, p=0.008). DEHP and DBP phthalates showed the highest risks for urogenital malformations (OR: 3.12, 95% CI: 1.45-6.72). First trimester exposure demonstrated the strongest associations across malformation types. GRADE evidence was rated as moderate to high for urogenital and cardiac anomalies but low for gastrointestinal and neural defects.

CONCLUSIONS: Prenatal ED exposure is significantly associated with increased risk of surgical congenital malformations, particularly male urogenital and cardiac anomalies. These findings support implementing preventive strategies during pregnancy and justify stricter regulatory policies to protect fetal health and reduce the surgical burden in pediatric populations.

LEVEL OF EVIDENCE: II (Systematic Review and Meta-Analysis).

PMID:41308826 | DOI:10.1016/j.jpedsurg.2025.162829


Associations of particulate matter size fractions and chemical composition with conjunctivitis and eczema: epidemiological evidence from the Pearl River Delta, China - November 27, 2025

Environ Res. 2025 Nov 25;289:123429. doi: 10.1016/j.envres.2025.123429. Online ahead of print.

ABSTRACT

Current evidence remains limited regarding the differential impact of particulate matter (PM) characteristics, such as size fraction and chemical composition, on allergic diseases. To address this, we recruited 131,346 school-aged children and adolescents from six cities of the Pearl River Delta (PRD) region of China from 2016 through 2018. PM of different size fractions (PM1, PM2.5 and PM10) and PM2.5 chemical composition (carbonaceous fractions, ions, metals and per- and polyfluoroalkyl substances; PFAS) were measured in ambient air. Conjunctivitis and eczema, two of the most common allergic conditions, were determined by self-reported doctor diagnosed affirmations from the parents or legal guardians. Logistic regression models were employed to explore associations between PM characteristics and allergic diseases. PM chemical composition was positively associated with both allergic diseases, while PM size fraction showed a positive association only with eczema. For example, per interquartile range (IQR) increase in PM1 (IQR = 3.75 μg/m3) concentrations showed an odds ratio (OR) of 1.19 (95 % CI: 1.15, 1.22) for eczema, and 0.97 (95 % CI: 0.91, 1.04) for conjunctivitis. In quantile g-computation (qg-comp) models, PM2.5 chemical composition was associated with higher risks of eczema (RR = 1.40, 95 % CI: 1.38, 1.42) and conjunctivitis (RR = 1.46, 95 % CI: 1.40, 1.53). Furthermore, these associations were robust in younger children, and in regions with low GDP or high population density. Our findings provide a nuanced understanding of how the size fraction and composition of PM exposure to the two most occurring allergic conditions.

PMID:41308899 | DOI:10.1016/j.envres.2025.123429


Preliminary Identification of PFAS and Other Emerging Contaminants in the French Broad River, NC Post-Hurricane Helene - November 27, 2025

Toxics. 2025 Oct 22;13(11):905. doi: 10.3390/toxics13110905.

ABSTRACT

Hurricanes are increasingly impacting inland water systems, yet their role in mobilizing anthropogenic contaminants remains insufficiently characterized. This study presents a preliminary assessment of organic contaminant loading in the French Broad River, North Carolina, 15 days after flooding from Hurricane Helene. Surface water samples from five sites were analyzed using liquid chromatography-high-resolution mass spectrometry. Targeted analysis quantified 11 per- and polyfluoroalkyl substances (PFASs), with summed concentrations ranging from 1.49 to 70.8 ng/L. One downstream site exhibited the highest burden, where PFOSs and PFOA exceeded U.S. EPA drinking water maximum contaminant levels. Non-targeted analysis (NTA) and suspect screening identified 468 compounds, with 96 structurally annotated at high confidence. Of these, a large proportion were associated with medium to high hazard potential, particularly for acute aquatic toxicity (69%), developmental toxicity (64%), mutagenic genotoxicity (49%), endocrine disruption (35%), skin irritation (27%), eye irritation (26%), and carcinogenicity (17%). Four EPA priority pollutants-4-nitrophenol, 2,4,6-trichlorophenol, pentachlorophenol, and dibutyl phthalate-were also detected. Site-specific chemical profiles suggested inputs from flood-damaged wastewater infrastructure and plastic debris. These findings highlight the susceptibility of freshwater systems to contaminant mobilization during extreme flooding and demonstrate the value of combining NTA and cheminformatics for post-disaster monitoring.

PMID:41304458 | PMC:PMC12656598 | DOI:10.3390/toxics13110905


Cardiotoxic Effect Induced by F-53B via Nitric Oxide Signalling on Parkin<sup>-/-</sup> Mice - November 27, 2025

Toxics. 2025 Oct 31;13(11):942. doi: 10.3390/toxics13110942.

ABSTRACT

A comprehensive understanding of gene-environment interactions is essential for maintaining human cardiac health, and deficiency in the key parkin gene exacerbates cardiac injury. Per- and polyfluoroalkyl substances (PFAS) exposure has been determined cardiotoxicity from the epidemiological perspective but the potential remained unclear. Here, we investigated the co-effects on cardiac pathological structure and function of an emerging PFAS, 6:2 chlorinated polyfluorinated ether sulfonate acid (F-53B), on male parkin-/- mice at dose of 3 and 3000 μg/kg for 60 d. Mechanism was focused on the activity, phosphorylation of endothelial nitric oxide synthase (eNOS), and the content of nitric oxide (NO), vital vascular function regulating molecule. F-53B significantly increased cardiac fibrosis to 1.58- and 2.80-fold, and cardiac troponin T (cTNT) to 1.17- and 1.32-fold compared with control group, at dose of 3 and 3000 μg/kg, respectively, indicating F-53B can inhibit the normal activities of the heart and cause functional disorders. Content and phosphorylation of eNOS significantly decreased to 0.68-, 0.67-fold, and to 0.65-, 0.54-fold compared with control group, respectively. The subsequent content of NO level was also significantly decreased to 0.47- and 0.33-fold, respectively, indicating that significant co-effects of parkin deficiency and F-53B exposure on cardiac function and structural changes via eNOS/NO signalling. Our work underscores the importance of assessing cardiac risk associated with PFAS at environmentally relevant doses, especially considering environmental exposure and gene co-interaction from the perspective of F-53B and parkin gene.

PMID:41304494 | PMC:PMC12655989 | DOI:10.3390/toxics13110942


Per- and Polyfluoroalkyl Substances (PFAS): History, Current Concerns, and Future Outlook - November 27, 2025

Molecules. 2025 Nov 14;30(22):4415. doi: 10.3390/molecules30224415.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) involve multiple per- and polyfluorinated compounds that are widely used globally. Legacy PFAS, including PFOA, PFOS, and PFHxS, were manufactured before 2000 in various industrialized nations, then gradually phased out in accordance with the Stockholm Convention. Due to the substantial accumulation of these legacy PFAS compounds, their concentrations in drinking water are regulated in some countries. This review first summarizes the historical background of PFAS, followed by a description of their chemical properties. The clinical manifestations of legacy PFAS in humans, such as dyslipidemia, attenuated immune function, and chronic kidney disorders, are also summarized. Emerging PFAS involve Gen-X and F-53B as well as numerous newly developed chemicals with their associated precursors/metabolites, including volatile PFAS. Research on these emerging PFAS compounds in the environment continues to grow, building a substantial body of evidence about their effects. The chemical structure of emerging PFAS shows a wide variety: they could contain ether, ester, sulfoneamide, and other halogen atoms rather than fluorine. Volatile PFAS involve the fluorotelomer 6:2 FTOH and other short-chain PFAS compounds, which are best measured by GC-MS. This review also briefly summarizes the assay for total oxidizable precursors of PFAS, an LC-MS-based assay for an emerging assay that will be used for a quantitative estimation of total PFAS, including emerging PFAS.

PMID:41302472 | PMC:PMC12655774 | DOI:10.3390/molecules30224415


Molecular Determinants of Per- and Polyfluoroalkyl Substances Binding to Estrogen Receptors - November 27, 2025

Toxics. 2025 Oct 22;13(11):903. doi: 10.3390/toxics13110903.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organofluorines linked to cancer, organ dysfunction, and other health problems. This study used quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) modeling to examine the binding of PFAS to estrogen receptor alpha (ERα) and beta (ERβ). Molecular docking of 14,591 PFAS compounds was performed, and docking scores were used as a measure of receptor affinity. QSPR models were built for two datasets: the ERα and ERβ top binders (TBs), and a set of commonly exposed (CE) PFAS. These models quantified how chemical descriptors influence binding affinity. Across the models, higher density and electrophilicity indicated positive correlations with affinity, while surface tension indicated negative correlations. Electrostatic descriptors, including HOMO energy and positive Fukui index (F+ max), were part of the models but showed inconsistent trends. The CE QSPR models displayed correlations that conflicted with those of the TB models. Following QSPR analysis, 66 QSAR models were developed using a mix of top binders and experimental data. These models achieved strong performance, with R2 values averaging 0.95 for training sets and 0.78 for test sets, that indicated reliable predictive ability. To improve generalizability, large-set QSAR models were created for each receptor. After outlier removal, these models reached R2 values of 0.68-0.71, which supports their use in screening structurally diverse PFAS. Overall, QSPR and QSAR analyses reveal key chemical features that influence PFAS-ER binding. This predictive approach provides a scalable framework to assess the binding interactions of structurally diverse PFAS to ERs and other nuclear receptors. All the codes, data, and the GUI visualization of the results are freely available at sivaGU/QSPR-QSAR-Molecular-Visualization-Tool.

PMID:41304455 | PMC:PMC12655904 | DOI:10.3390/toxics13110903


Preliminary Identification of PFAS and Other Emerging Contaminants in the French Broad River, NC Post-Hurricane Helene - November 27, 2025

Toxics. 2025 Oct 22;13(11):905. doi: 10.3390/toxics13110905.

ABSTRACT

Hurricanes are increasingly impacting inland water systems, yet their role in mobilizing anthropogenic contaminants remains insufficiently characterized. This study presents a preliminary assessment of organic contaminant loading in the French Broad River, North Carolina, 15 days after flooding from Hurricane Helene. Surface water samples from five sites were analyzed using liquid chromatography-high-resolution mass spectrometry. Targeted analysis quantified 11 per- and polyfluoroalkyl substances (PFASs), with summed concentrations ranging from 1.49 to 70.8 ng/L. One downstream site exhibited the highest burden, where PFOSs and PFOA exceeded U.S. EPA drinking water maximum contaminant levels. Non-targeted analysis (NTA) and suspect screening identified 468 compounds, with 96 structurally annotated at high confidence. Of these, a large proportion were associated with medium to high hazard potential, particularly for acute aquatic toxicity (69%), developmental toxicity (64%), mutagenic genotoxicity (49%), endocrine disruption (35%), skin irritation (27%), eye irritation (26%), and carcinogenicity (17%). Four EPA priority pollutants-4-nitrophenol, 2,4,6-trichlorophenol, pentachlorophenol, and dibutyl phthalate-were also detected. Site-specific chemical profiles suggested inputs from flood-damaged wastewater infrastructure and plastic debris. These findings highlight the susceptibility of freshwater systems to contaminant mobilization during extreme flooding and demonstrate the value of combining NTA and cheminformatics for post-disaster monitoring.

PMID:41304458 | PMC:PMC12656598 | DOI:10.3390/toxics13110905


Occurrence and fate of PTE, PAH, and PFAS trace contaminants in soils and river suspended particulate matter in three DANUBEAN river catchments - November 27, 2025

J Environ Qual. 2026 Jan-Feb;55(1):e70116. doi: 10.1002/jeq2.70116.

ABSTRACT

This study aimed to investigate the occurrence and concentration patterns of three groups of trace contaminants-potentially toxic elements (PTEs), polycyclic aromatic hydrocarbons (PAHs), and per- and polyfluoroalkyl substances (PFASs)-in river catchments with contrasting land use and landscape characteristics. A second objective was to relate the concentrations in suspended particulate matter (SPM) to those in soils and to catchment attributes in order to identify dominant transport processes and contaminant sources. A spatially explicit monitoring campaign was conducted in three river catchments of the central Danube River Basin: Zagyva and Koppány in Hungary and Wulka in Austria. Composite soil samples (∼10 per catchment, totaling ∼200 subsamples) were collected from forest, pasture, and cropland areas. SPM was collected using both passive and active samplers under base-flow and high-flow conditions. The results revealed strong spatial variability in concentrations for five of seven PTEs, all PAHs, and eight of 10 PFASs. Substances predominantly deposited atmospherically-such as PAHs and several PFASs-were more concentrated in forest soils compared to pasture and cropland. Base-flow SPM samples were often more contaminated than high-flow samples, especially for PAHs and some PTEs. Concentrations in SPM were generally correlated with soil concentrations, suggesting that erosion-related transport of these chemicals may be significant in rural catchments. However, enrichment patterns and correlation strength varied by substance group and land use type. These findings support the use of parallel SPM and soil sampling for improving empirical emission modeling and source identification in catchments with mixed land use.

PMID:41299797 | PMC:PMC12657677 | DOI:10.1002/jeq2.70116


Molecular Determinants of Per- and Polyfluoroalkyl Substances Binding to Estrogen Receptors - November 27, 2025

Toxics. 2025 Oct 22;13(11):903. doi: 10.3390/toxics13110903.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organofluorines linked to cancer, organ dysfunction, and other health problems. This study used quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) modeling to examine the binding of PFAS to estrogen receptor alpha (ERα) and beta (ERβ). Molecular docking of 14,591 PFAS compounds was performed, and docking scores were used as a measure of receptor affinity. QSPR models were built for two datasets: the ERα and ERβ top binders (TBs), and a set of commonly exposed (CE) PFAS. These models quantified how chemical descriptors influence binding affinity. Across the models, higher density and electrophilicity indicated positive correlations with affinity, while surface tension indicated negative correlations. Electrostatic descriptors, including HOMO energy and positive Fukui index (F+ max), were part of the models but showed inconsistent trends. The CE QSPR models displayed correlations that conflicted with those of the TB models. Following QSPR analysis, 66 QSAR models were developed using a mix of top binders and experimental data. These models achieved strong performance, with R2 values averaging 0.95 for training sets and 0.78 for test sets, that indicated reliable predictive ability. To improve generalizability, large-set QSAR models were created for each receptor. After outlier removal, these models reached R2 values of 0.68-0.71, which supports their use in screening structurally diverse PFAS. Overall, QSPR and QSAR analyses reveal key chemical features that influence PFAS-ER binding. This predictive approach provides a scalable framework to assess the binding interactions of structurally diverse PFAS to ERs and other nuclear receptors. All the codes, data, and the GUI visualization of the results are freely available at sivaGU/QSPR-QSAR-Molecular-Visualization-Tool.

PMID:41304455 | PMC:PMC12655904 | DOI:10.3390/toxics13110903


Perfluoroalkyl Substances (PFAS) and Lipid Metabolism in Experimental Animal Models: A Scoping Review on the Mechanisms Behind the Induced Hepatotoxicity - November 26, 2025

Curr Issues Mol Biol. 2025 Nov 13;47(11):944. doi: 10.3390/cimb47110944.

ABSTRACT

Per and polyfluoroalkyl substances (PFAS) are a class of synthetic, persistent environmental pollutants detected in biological systems and increasingly recognized for their harmful effects on human health. The liver, being a central organ in the metabolism of xenobiotics, is profoundly affected by these compounds and is a main target of PFAS-induced toxicity. The purpose of the present Scoping Review is to investigate the multiple and complex mechanisms behind PFAS hepatotoxicity, taking into consideration evidence from preclinical in vivo models. Using electronic databases (PubMed and Google Scholar), a total of 38 studies were found eligible to be extensively explored to gather information regarding PFAS toxicity toward hepatic lipid metabolism, oxidative stress, injury and inflammation. Moreover, the parental exposure of these chemicals on the offspring will be discussed as well. As illustrated in the proposed graphical abstract, PFAS exposure has been linked to the triggering of oxidative stress phenomena, mitochondrial dysfunction and hepatic inflammatory infiltrate with sex specific effects in rodents. The predominant effects manifest as the overproduction of reactive oxygen species (ROS), the disruption of hepatic lipid metabolism, and the activation of several nuclear transcription factors involved in lipid regulation, with PPAR-α being the most prominent. Considering their strong bioaccumulative properties and persistence in both the environment and the human body, legacy and emerging PFAS should be regarded as potent toxicants with a distinctive role in the onset of metabolic diseases and as a pressing issue to be addressed within regulatory policies.

PMID:41296448 | PMC:PMC12650804 | DOI:10.3390/cimb47110944


Per- and polyfluoroalkyl substances (PFAS) in urbanized coastal zones: spatiotemporal distribution, phase partitioning dynamics, and risk assessment in Shenzhen, China - November 26, 2025

Environ Int. 2025 Nov 21;206:109956. doi: 10.1016/j.envint.2025.109956. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants of global concern. This study investigated the occurrence of 29 PFAS compounds across dissolved phase, suspended particulate matter (SPM), and surface sediment in four coastal zones of Shenzhen, China-a megacity undergoing intensive development. Results revealed widespread PFAS contamination, with total concentrations ranging from 4.306-53.716 ng/L (dissolved phase), 0.30-22.259 ng/L (SPM), and 0.561-20.354 ng/g (sediment). Short-chain perfluoroalkyl carboxylates (PFCAs, C4-C6) dominated aqueous phases (58.5% of Σ29PFAS), while long-chain PFCAs (≥C7) prevailed in SPM (68.1%) and sediments (69.4 %), reflecting chain-length-dependent partitioning. Spatial analysis identified the Pearl River Estuary (PRE) as a PFAS hotspot, with levels 2.5-3.5 times higher than adjacent bays, probably linked to fluvial inputs from industrial and urban sources. Historical data for the PRE further revealed contrasting temporal trends: PFOS concentrations declined markedly from 33.91 ng/L in 2012 to 2.06 ng/L in 2020, consistent with global phase-out measures, whereas PFOA levels peaked in 2020 (27.73 ng/L) before decreasing to 1.88 ng/L in 2023, likely reflecting its initial use as a PFOS substitute and subsequent regulatory control. Sediment-water partitioning coefficients (log Kd) increased by 0.33-0.35 log units per CF2 moiety, highlighting hydrophobic interactions as the key driver. Ecological risk assessment indicated low-to-moderate risks (RQs: 0.003-0.155), with PFOS in sediments near airports and industrial zones of PRE posing localized concerns. As the first comprehensive and systematic study on PFAS in the Shenzhen coastal area, this work provides novel insights into the distribution, partitioning behavior, and ecological risks of these persistent environmental contaminants. The findings underscore the need for source-specific management strategies to mitigate PFAS impacts in coastal urban environments.

PMID:41297193 | DOI:10.1016/j.envint.2025.109956


Sediment-specific microbial nitrogen cycling disruption by fluoroalkylether substitutes: HFPO-DA and PF4OPeA exert divergent mechanisms - November 26, 2025

J Hazard Mater. 2025 Nov 24;500:140612. doi: 10.1016/j.jhazmat.2025.140612. Online ahead of print.

ABSTRACT

Fluoroalkylether substances (ether-PFASs), emerging substitutes for legacy PFASs, exhibit increasing marine sediment contamination comparable to traditional PFASs, yet their specific impacts on microbial nitrogen cycling remain poorly understood. This study reveals compound-specific mechanisms by which two ether-PFASs (Heptafluoropropylene oxide dimer acid (HFPO-DA) and Perfluoro (3-methoxy) propionic acid (PF4OPeA)) disrupt nitrogen transformations in three Pacific sediments across environmental concentrations (0.01-100 μg/g). HFPO-DA significantly altered nitrification rates in sediment- and concentration-dependent manners while consistently promoting nitrite reductase (NiR) activity by 0.5-20.5 % across all sediments. Conversely, PF4OPeA primarily stimulated nitrification but exerted divergent effects on NiR that were critically dependent on the sediment habitat, ranging from promotion to universal inhibition. Structural equation modeling (SEM) identified fundamentally distinct pathways: HFPO-DA directly regulated nitrification via sediment-modulated ammonia-oxidizing bacteria (AOB) amoA gene abundance and denitrification through nirS/nirK genes. In contrast, PF4OPeA modulated nitrification by first altering bacterial α-diversity, which subsequently influenced AOB amoA, while its denitrification effects propagated through a cascade involving sediment properties, α-diversity, nirS, and NiR activity (p < 0.05). These results establish that ether-PFASs subvert nitrogen cycling via divergent mechanisms: HFPO-DA targets functional genes directly, whereas PF4OPeA acts through microbial community restructuring, with sediment properties dictating ecotoxicity and critically mediating both outcomes. This work thereby provides a critical basis for ecological risk assessment of PFAS alternatives in marine environments.

PMID:41297262 | DOI:10.1016/j.jhazmat.2025.140612


Unlocking the potential of bioelectrokinetic interfaces in remediation of organohalide pollutants in low-permeability soils - November 26, 2025

Water Res. 2025 Nov 22;289(Pt B):125019. doi: 10.1016/j.watres.2025.125019. Online ahead of print.

ABSTRACT

Organohalide contamination in low-permeability soils poses a formidable challenge to in situ bioremediation due to the limitations of mass transport and microbial activity. This review highlights electrokinetic-enhanced bioremediation (EK-BIO) as a transformative strategy that integrates electrokinetic transport with microbial metabolism at electrode-microbe interfaces. We dissect the mechanistic contributions of electromigration, electroosmosis, and electrophoresis in mobilizing nutrients, microbes, and pollutants, and evaluate how electric fields modulate microbial viability and microenvironment to optimize degradation of organohalide pollutants. Beyond enhancing transport, EK-BIO catalyzes hybrid degradation via direct electron transfer, reactive species oxidation, and electrode-mediated microbial processes. By synthesizing laboratory and field-scale applications of EK-BIO, we identify key technical and operational challenges in the remediation of chlorinated solvents, which remain the primary focus of EK-BIO research. Although preliminary findings indicate potential applicability to emerging contaminants such as per- and polyfluoroalkyl substances (PFAS), current evidence remains limited and exploratory. Finally, we outline future directions for scaling EK-BIO, including system optimization, design of resilient microbial consortia, advanced electrode materials, and the establishment of a standardized implementation procedure. This review provides a critical roadmap for advancing EK-BIO as a next-generation, sustainable technology for remediating persistent organohalide pollutants in complex subsurface environments.

PMID:41297309 | DOI:10.1016/j.watres.2025.125019


Effects of per- and polyfluoroalkyl substances on molecular initiating events of cholestatic liver injury - November 26, 2025

Sci Total Environ. 2025 Nov 25;1008:180975. doi: 10.1016/j.scitotenv.2025.180975. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are abundantly used in a plethora of products with applications in daily life. As a result, PFAS are widely distributed in the environment, raising concerns regarding accumulation in humans. Recent data show impairment of bile acid metabolism by legacy PFAS, yet the potential of short-chain and alternative PFAS as well as the mechanistic basis of these cholestatic effects remain elusive. The present study relied on an in vitro test battery mechanistically anchored in an adverse outcome pathway network to assess the cholestatic potential of legacy, short-chain and alternative PFAS. Focus was put on the effects of PFAS on molecular initiating events, in particular transporter changes and bile canaliculi dynamics. Cultures of human HepaRG liver cells were exposed to 8 types of PFAS in 3 concentrations. Fluorescently labeled probes were used to investigate effects on the functionality of bile acid transporters. Effects at the transcriptional level were studied by means of quantitative reverse transcriptase polymerase chain reaction analysis. Bile canaliculi dynamics were monitored via in situ immunostaining and phase-contrast imaging. An integrated weight-of-evidence approach was applied to process the results of the in vitro test battery. PFAS inhibit the expression and activity of various bile acid transporters, including organic anion transporting polypeptides and multidrug resistance-associated proteins. Some PFAS inflicted morphological disruption of bile canaliculi. The highest overall cholestatic scores were observed for perfluorononanoic acid, perfluorooctane sulfonic acid and perfluorobutanoic acid, while C6 PFAS exhibited low cholestatic potential. This study shows the power of in vitro testing to elucidate mechanisms underlying hepatotoxicity induced by PFAS and, simultaneously, to quantify the cholestatic potential of these ubiquitous "forever chemicals".

PMID:41297488 | DOI:10.1016/j.scitotenv.2025.180975


Leachate recirculation to reduce PFAS discharge from landfills - November 26, 2025

Sci Total Environ. 2025 Nov 25;1008:181010. doi: 10.1016/j.scitotenv.2025.181010. Online ahead of print.

ABSTRACT

Given the persistent challenge of PFAS removal from chemically complex landfill leachate, this study investigates leachate recirculation to increase PFAS retention within landfilled materials. The lab-scale column reactor findings suggest that leachate recirculation enhances the sorption removal of anionic PFAS in landfill organics and plastics, leading to PFAS reduction. Using eleven PFAS compounds (i.e., nine carboxylates and two sulfonates) at different concentrations, we demonstrated that PFAS concentrations in landfill organics increased by 134-1000 times and on polyethylene plastics increased by 37-329 times after twelfth recirculation. PFAS removal was significantly higher as carbon chain length and Log Koc values increased. No PFAS with eight or more carbons were detected in the recirculated leachate (except for PFOA: 88-96 % removal) after six and twelfth recirculation. Short-chain PFAS (C ≤ 7) were retained at 20-65 % after twelfth recirculation. The leachate PFAS levels either decreased or stayed the same after the twelfth recirculation, indicating no desorption of PFAS from organics and plastics under experimental conditions. Mass balance showed total PFAS in organics, leachate, and plastics matched initial reactor load. These findings demonstrate that extremely high concentrations of PFAS can be effectively removed from leachate through proper recirculation within landfills. However, future large-scale studies in real-world landfills are needed to assess the performance and feasibility of this approach.

PMID:41297491 | DOI:10.1016/j.scitotenv.2025.181010


Integrated assessment of the effects of PFOA exposure on hepatic transcriptome and lipid profiles in mice expressing human PPARα - November 26, 2025

Toxicol Appl Pharmacol. 2025 Nov 24:117658. doi: 10.1016/j.taap.2025.117658. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are a family of persistent chemicals that continue to be released pervasively into the environment, leading to widespread human exposure. Emerging epidemiological evidence shows adverse effects on liver lipids; however, past toxicological studies have been limited by a focus on peroxisome proliferator activated receptor α (PPARα) driven effects on triglycerides in rodent systems. Here, we use a more agonostic approach incorporating lipidomics and transcriptomics to test the hypothesis that activation of human PPARα by PFOA, disrupts liver lipid homeostasis, broadly, similar to that seen in human liver diseases. Female and male mice expressing human PPAR α or that were PPARα null were fed a What We Eat In America diet and exposed to PFOA via drinking water for 6 weeks. Serum PFOA concentrations averaged 48 ± 9 μg/mL. PFOA changed the expression of ~2000 hepatic genes with expression of a larger number of genes in hPPARα versus PPARα null mice. In this occupational level PFOA exposure scenario, less than 60 % of transcriptional changes induced by PFOA depended on PPARα expression. CAR was another major molecular initiating event, with other transcription factors pathways more likely to be modulated downstream of hPPARα activation. In hPPARα mice of both sexes, PFOA increased total liver lipids. In addition to triacylglycerides, lipid classes strongly altered by PFOA exposure predominantly belong to phosphatidylcholine and sphingolipid classes. PFOA significantly decreased sphingomyelin abundance and increased ceramide abundance regardless of genotype, which coincided with an increase in expression of SMase, the enzyme that converts sphingomyelin to ceramide. These results highlight the ability of PFOA to modulate liver lipids beyond triacylglycerides in both an hPPARα-dependent and -independent manner.

PMID:41297771 | DOI:10.1016/j.taap.2025.117658


Polypropylene nanoplastics as PFAS carriers: A computational study of the adsorption mechanism - November 26, 2025

Environ Pollut. 2025 Nov 24;389:127434. doi: 10.1016/j.envpol.2025.127434. Online ahead of print.

ABSTRACT

Polypropylene (PP) is a major constituent of nanoplastics (NPs) found worldwide in aquatic environments, where it promotes the co-transport of contaminants. Of particular concern is the co-transport of perfluoroalkyl substances (PFAS), potentially increasing the uptake and bioaccumulation of PFAS in organisms during simultaneous exposure. Since the adsorption mechanism of PFAS molecules on NPs is still only partially understood, we have carried out a thorough systematic investigation of how a range of PFAS interact with PP nanoplastics. To this end, we developed a computational procedure which combines molecular mechanics, semiempirical methods and density functional theory calculations. We were able to describe quantitatively the adsorption process, revealing similarities and differences in the adsorption behavior as a function of the PFAS length, branching and of the nature of the PFAS polar head. Our findings suggest that the nanoplastic possess a certain degree of local flexibility which allows it to effectively adsorb all the investigated compounds, by modifying its form to maximize the interactions with PFAS. The adsorption mechanism is mainly driven by dispersion forces between the PFAS perfluorinated chain and the nanoplastic polymeric chain, with minor electrostatic contributions. These findings represent a significant step forward in the rationalization of PFAS adsorption behavior, which is essential not only to clarify their environmental fate but also to help develop strategies for PFAS removal from contaminated water sources.

PMID:41297869 | DOI:10.1016/j.envpol.2025.127434


Discovery of Previously Unreported Per- and Polyfluoroalkyl Substances (PFAS) in Pooled Australian Human Serum Using Nontarget Analysis - November 26, 2025

Environ Sci Technol. 2025 Nov 26. doi: 10.1021/acs.est.5c04623. Online ahead of print.

ABSTRACT

Humans may be exposed to thousands of per- and polyfluoroalkyl substances (PFAS), yet only a small fraction of these are regularly monitored, potentially underestimating the associated risks. This study employed high-resolution mass spectrometry (HRMS)-based nontarget analysis to investigate previously unreported PFAS in pooled serum from Australians. Samples collected between 2002 and 2021 from men aged > 30 years in the general population (GP, n = 27) and firefighters (FF, n = 18), categorized into three age groups (31-45, 46-60, and ≥ 60), were analyzed. Fourteen PFAS were identified or structurally annotated, including six known (level 1a-1b) and seven suspects (level 2b-3a). Additionally, six suspects with CHF2 or CF3 functionalities were tentatively annotated. Two previously unreported PFAS in human serum, hydrogen-substituted 2:1 perfluoroether sulfonic acid (2:1 H-PFESA) and hexafluoro-1,2-propanediol (HFPrD), were detected in 42% and 56% of samples, respectively. Further analysis of these two compounds in broader GP serum pools, including six age groups and both sexes, revealed their presence even in children under five, with relatively high intensities. No clear temporal, age, sex, or occupation-related trends were observed, suggesting widespread ongoing population exposure. These findings underscore the need for expanded HRMS-based monitoring to better assess human PFAS exposure.

PMID:41297907 | DOI:10.1021/acs.est.5c04623


Iron Redox Cycling in Persulfate Activation: Strategic Enhancements, Mechanistic Insights, and Environmental Applications-A Review - November 26, 2025

Nanomaterials (Basel). 2025 Nov 12;15(22):1712. doi: 10.3390/nano15221712.

ABSTRACT

Iron-based catalysts for peroxymonosulfate (PMS) and peroxydisulfate (PDS) activation represent a cornerstone of advanced oxidation processes (AOPs) in environmental remediation, prized for their cost-effectiveness, environmental compatibility, and high catalytic potential. These catalysts, including zero-valent iron, iron oxides, and iron-organic frameworks, activate PMS/PDS through heterogeneous and homogeneous pathways to generate reactive species such as sulfate radicals (SO4-) and hydroxyl radicals (•OH). However, their large-scale implementation is constrained by inefficient iron cycling, characterized by sluggish Fe3+/Fe2+ conversion and significant iron precipitation, leading to catalyst passivation and oxidant wastage. This comprehensive review systematically dissects innovative strategies to augment iron cycling efficiency, encompassing advanced material design through elemental doping, heterostructure construction, and defect engineering; system optimization via reductant incorporation, bimetallic synergy, and pH modulation; and external field assistance using light, electricity, or ultrasound. We present a mechanistic deep-dive into these approaches, emphasizing facilitated electron transfer, suppression of iron precipitation, and precise regulation of radical versus non-radical pathways. The performance in degrading persistent organic pollutants-including antibiotics, per- and polyfluoroalkyl substances (PFASs), and pesticides-in complex environmental matrices is critically evaluated. We further discuss practical challenges related to scalability, long-term stability, and secondary environmental risks. Finally, forward-looking directions are proposed, focusing on rational catalyst design, integration of sustainable processes, and scalable implementation, thereby providing a foundational framework for developing next-generation iron-persulfate catalytic systems.

PMID:41295619 | PMC:PMC12655755 | DOI:10.3390/nano15221712


Perfluorooctanesulfonamide-induced epiboly delay is associated with decreased ATP production within zebrafish embryos - November 26, 2025

Ecotoxicol Environ Saf. 2025 Nov 25;307:119479. doi: 10.1016/j.ecoenv.2025.119479. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) persistence within environmental media has led to ubiquitous exposure within humans and wildlife. We previously found that exposure of zebrafish embryos to perfluorooctanesulfonamide (PFOSA) from 0.75 to 6 h post-fertilization (hpf) resulted in a concentration-dependent delay in epiboly - a critical developmental landmark in fish and amphibian species. Therefore, for this study, we explored whether 1) similar mechanisms underlie epiboly delays induced by PFOSA or Cytochalasin B (CCB), a potent inhibitor of actin polymerization that disrupts normal epiboly progression, and 2) PFOSA-induced epiboly delay is associated with a decrease in embryonic ATP, as PFOSA is a potent uncoupler of oxidative phosphorylation in vitro. Although PFOSA and CCB induced a similar magnitude of epiboly delay beginning at 4 hpf following initiation of exposure at 0.75 hpf, PFOSA did not, contrary to CCB, significantly decrease yolk-associated actin within embryos. Using mRNA-sequencing, we also found that, consistent with chemical-specific differences in effects on actin polymerization, PFOSA-exposed embryos were also transcriptionally different from CCB-exposed embryos. Moreover, phenotypically matched, PFOSA-exposed embryos at 6 hpf were transcriptionally similar to vehicle-exposed embryos at 5 hpf, and PFOSA delayed the maternal-to-zygotic transition (MZT) beginning at 5 hpf. Finally, PFOSA-induced delayed epiboly was associated with decreased ATP concentrations, an effect that was partially mitigated by co-exposure to exogenous ATP. Overall, our findings suggest that PFOSA exposure during early embryonic development decreases ATP production in the absence of effects on actin polymerization in vivo, an effect that is associated with PFOSA-induced delays in epiboly and the MZT.

PMID:41297289 | DOI:10.1016/j.ecoenv.2025.119479


Mobile genetic elements and wastewater treatment: contaminants of emerging concern, climate change, and trophic transmission - November 26, 2025

Front Microbiol. 2025 Nov 10;16:1699325. doi: 10.3389/fmicb.2025.1699325. eCollection 2025.

ABSTRACT

This minireview focuses on recent developments regarding mobile genetic elements (MGEs) and horizontal gene transfer (HGT) in wastewater treatment plants (WWTPs) and proximal environments. WWTPs are often discussed as hotspots and bioreactors for the evolution of MGEs and ARGs and their horizontal transfer. Firstly, the article reviews the effects of emerging contaminants on HGT and MGEs with a specific focus on microplastics and per- and polyfluoroalkyl substances (PFAS). Secondly, the review focuses on how extreme weather and climate change can overwhelm WWTPs, increase the input of diverse genetic elements, and alter the dynamics of HGT. Finally, the trophic connections between the WWTP microbiota and external ecosystems underscore the potential for wider transmission of MGEs. Here, the focus is on transfer of MGEs to larger organisms in the vicinity of WWTPs. In sum, the review focuses on emerging areas of research that refine our understanding of the WWTP environment as a hotspot for HGT and dissemination of MGEs with potentially deleterious implications for human and wider ecosystem health.

PMID:41292681 | PMC:PMC12643467 | DOI:10.3389/fmicb.2025.1699325


Computational Toxicology to Elucidate PFASs Causing Fetal Growth Restriction via Binding to and Degrading IGF1 Protein - November 26, 2025

Environ Sci Technol. 2025 Nov 25. doi: 10.1021/acs.est.5c05620. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) have been associated with fetal growth restriction (FGR), although the underlying mechanisms remain elusive. Using computational toxicology, we identified 17 commercially prevalent PFASs that exhibit high absorption potential but are poorly metabolized and excreted. These compounds destabilize insulin-like growth factor 1 (IGF1) protein and disrupt the PI3K-AKT signaling pathway, thereby contributing to FGR. Specifically, molecular docking analysis revealed that PFASs can bind to the interaction region of IGF1 and IGF-binding proteins (IGFBPs) with perfluorodecanoic acid (PFDA), perfluorooctanesulfonate (PFOS), and perfluorononanoic acid (PFNS) showing the strongest binding affinities. Molecular dynamics simulations further revealed that PFDA, PFOS, and PFNS maintain stable conformational dynamics upon binding to IGF1, characterized by strong binding free energies and intermolecular forces similar to those of the original ligand. In vitro experiments confirmed that PFDA and PFOS form highly stable complexes with IGF1 protein at nanomolar affinities, reduce extracellular IGF1 protein levels, and inhibit trophoblast cell proliferation. Notably, supplementation with the recombinant IGF1 protein significantly ameliorated these adverse effects. Collectively, the present study has elucidated IGF1 as a direct target mediating PFAS-induced FGR with PFDA, PFOS, and PFNS playing significant roles, which provides novel insights for the development of preventive and therapeutic strategies targeting PFAS-related developmental disorders.

PMID:41292105 | DOI:10.1021/acs.est.5c05620


Poly-/Perfluoroalkyl Substance (PFAS) Immobilization Using a Novel Adsorptive Organoclay Compared with Colloidal-Activated Carbon in Soil under Dynamic Redox Conditions and the Response of Microbial Communities - November 26, 2025

ACS Omega. 2025 Nov 4;10(45):54441-54454. doi: 10.1021/acsomega.5c07196. eCollection 2025 Nov 18.

ABSTRACT

Poly-/perfluoroalkyl substance (PFAS) contamination is a significant global environmental concern and requires effective remediation solutions. Although it is often assumed that PFAS sorption is not redox sensitive, redox fluctuations can significantly modify the biogeochemical environment, influencing PFAS behavior indirectly. This study evaluated the effectiveness of soil amendments, a novel adsorptive organoclay (AOC) and a colloidal-activated carbon (CAC) on PFAS immobilization under dynamic redox conditions. PFAS-contaminated soil was treated with AOC and CAC. We created a slurry, set systematically five predefined redox windows (from -100 to +500 mV), and collected samples at each redox window. PFAS concentrations were measured in the dissolved phase (<0.45 μm), and phospholipid fatty acid (PLFA) was analyzed in the solid phase (>0.45 μm). The contaminated soil contained 13 PFAS compounds. CAC treatment drastically reduced the dissolved PFAS concentrations across all redox windows compared to the control and AOC treatment. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), perfluorononanoic acid (PFNA), and 6:2 fluorotelomer sulfonamide propyl betaine (6:2 FTAB) dominated in the dissolved phase of control and AOC treatment. The dissolved phase of CAC mainly contained shorter-chain perfluoropentanoic acid (PFPeA) and perfluorobutanoic acid (PFBA). The specific surface area (SSA) along with total carbon (TC) content of amendments are key factors in reducing PFAS concentration in the dissolved phase. Relatively similar PLFA profiles indicated no adverse effects on soil microbial community from either amendment compared to the control. This study highlights CAC as an effective amendment for PFAS immobilization even under changing environmental redox conditions.

PMID:41292558 | PMC:PMC12643322 | DOI:10.1021/acsomega.5c07196


Mobile genetic elements and wastewater treatment: contaminants of emerging concern, climate change, and trophic transmission - November 26, 2025

Front Microbiol. 2025 Nov 10;16:1699325. doi: 10.3389/fmicb.2025.1699325. eCollection 2025.

ABSTRACT

This minireview focuses on recent developments regarding mobile genetic elements (MGEs) and horizontal gene transfer (HGT) in wastewater treatment plants (WWTPs) and proximal environments. WWTPs are often discussed as hotspots and bioreactors for the evolution of MGEs and ARGs and their horizontal transfer. Firstly, the article reviews the effects of emerging contaminants on HGT and MGEs with a specific focus on microplastics and per- and polyfluoroalkyl substances (PFAS). Secondly, the review focuses on how extreme weather and climate change can overwhelm WWTPs, increase the input of diverse genetic elements, and alter the dynamics of HGT. Finally, the trophic connections between the WWTP microbiota and external ecosystems underscore the potential for wider transmission of MGEs. Here, the focus is on transfer of MGEs to larger organisms in the vicinity of WWTPs. In sum, the review focuses on emerging areas of research that refine our understanding of the WWTP environment as a hotspot for HGT and dissemination of MGEs with potentially deleterious implications for human and wider ecosystem health.

PMID:41292681 | PMC:PMC12643467 | DOI:10.3389/fmicb.2025.1699325


Developmental exposure to a PFAS mixture impairs the anamnestic response to influenza A virus infection in mice - November 26, 2025

bioRxiv [Preprint]. 2025 Nov 12:2025.11.10.687657. doi: 10.1101/2025.11.10.687657.

ABSTRACT

Developmental exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to reduced antibody responses to childhood vaccines, but the underlying mechanisms remain unclear. Antibody production relies on interactions between various immune cell types, and it is unknown which are affected by PFAS exposure during development. To investigate this in a human-health relevant system, an in vivo model was established to delineate effects of developmental exposure to a mixture of four PFAS commonly found in human serum: PFOA, PFOS, PFHxS, and PFNA. Pregnant mice consumed water containing these PFAS throughout gestation and lactation. PFAS were measured in both mothers and offspring, and an exposure that avoided overt health issues was selected. The immune response to influenza A virus (IAV) infection was assessed in male and female offspring. Results showed that developmental PFAS exposure reduced IAV-specific antibody levels in both sexes. However, it diminished T follicular helper cells and germinal center B cells-critical for antibody production-in only female offspring. These findings highlight possible sex-specific immune effects and identify potential cellular mechanisms behind reduced antibody levels. Since these immune cells are essential for antibody production in humans, this study provides valuable insights into how PFAS exposure may impact human health.

SYNOPSIS: A novel mouse model of developmental exposure to a human-relevant PFAS mixture recapitulates observations in epidemiological studies and also provides new insight into potential mechanisms of the lower antibody levels observed in humans.

PMID:41292798 | PMC:PMC12642599 | DOI:10.1101/2025.11.10.687657


A Novel Constrained Drop Surfactometer Demonstrates Inhibition of Lung Surfactant Function by PFAS Aerosols In Vitro - November 25, 2025

Toxicol Sci. 2025 Nov 25:kfaf156. doi: 10.1093/toxsci/kfaf156. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in both indoor and outdoor air, and there is increasing need to effectively screen this diverse class of chemicals for inhalation toxicity potential. Since PFAS have strong surface-active properties, we hypothesized they may interfere with lung surfactant (LS) activity. We investigated the ability of 17 PFAS delivered as liquid aerosols to inhibit LS function in a newly developed constrained drop surfactometer (CDS). Using both fluorescent tracers and mass spectrometry techniques, deposition of PFAS aerosols onto exposed LS was determined. Nine of the 17 PFAS increased surface tension (ST) above the inhibition threshold, defined as mean minimum post-exposure ST above 10 mN/m. Inhibitory compounds included legacy PFAS (perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)), emerging compounds (hexafluoropropylene oxide dimer acid, perfluoro-2-methoxyacetic acid), perfluorooctyltriethoxysilane, and perfluorooctane-sulfonamides and -sulfonamidoethanols. These compounds represent a wide range of molecular weights and functional head groups (carboxylic and sulfonic acids, sulfonamides, and siloxane). Among these compounds, the lowest modeled inhibitory doses were for N-methyl-perfluorooctane-sulfonamidoethanol (0.34 ppm) and N-ethyl-perfluorooctane-sulfonamidoethanol (0.14 ppm). Concentrations of PFOA and PFOS required to inhibit LS were significantly lower when aerosolized than when directly mixed with LS, demonstrating the importance of interactions with surfactant at the air-liquid interface. Our results show that a combination of size, functional groups, and hydrophobicity influence the ability of PFAS to inhibit LS function. Under high exposure conditions, inhaled PFAS may initiate an adverse outcome pathway through surfactant inhibition, which may ultimately produce a reduction of lung function.

PMID:41289147 | DOI:10.1093/toxsci/kfaf156


Endocrine Disrupting Chemicals in Human Milk: A Systematic Review of Concentrations and Potential Health Implications - November 25, 2025

Curr Environ Health Rep. 2025 Nov 25;12(1):48. doi: 10.1007/s40572-025-00515-5.

ABSTRACT

PURPOSE OF REVIEW: Endocrine-disrupting chemicals (EDCs) disrupt the synthesis, transport, action, or metabolism of endogenous hormones in the human body. EDCs often enter the body through inhalation, ingestion, or dermal contact and can accumulate in the body. Remobilization or transfer of EDCs can occur during lactation, causing human milk to become contaminated with a variety of EDCs, which could expose nursing infants and children to these chemicals.

RECENT FINDINGS: Several studies have examined the concentration ranges for one or multiple EDC(s) in human milk. Additional studies document associations between EDC exposure and adverse health outcomes, many of which are in adult populations. It is therefore essential to understand the extent to which EDCs in human milk contribute to cumulative early-life exposures.

SUMMARY: We performed a literature review of peer-reviewed studies reporting concentrations of one or more of the following EDCs in human milk during or after 2004: bisphenols, organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), parabens, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and phthalates. We identified concentration ranges for each chemical detected in human milk and health impacts associated with early-life exposures to EDCs noted across studies from this review. Determining the presence of EDCs in human milk and the associated effects of exposure through nursing is essential to develop feeding recommendations that safeguard infant and child health.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40572-025-00515-5.

PMID:41286197 | PMC:PMC12644229 | DOI:10.1007/s40572-025-00515-5


A meta-analysis-based adverse outcome pathway for the reproductive toxicity induced by per- and poly-fluoroalkyl substances in animals - November 25, 2025

Toxicology. 2025 Nov 23;520:154352. doi: 10.1016/j.tox.2025.154352. Online ahead of print.

ABSTRACT

Per- and poly-fluoroalkyl substances (PFAS) were highly toxic to reproductive systems due to the widespread environmental distribution and persistence. However, the underlying mechanisms were not well understood. This study systematically evaluated the association between existing adverse outcome pathways (AOPs) and PFAS-induced reproductive toxicity using the AOP conceptual framework. A meta-analysis of 28 studies quantified the effect sizes, providing a comprehensive assessment of PFAS-induced reproductive toxicity in animals. Within the AOP framework, the molecular initiating event (MIE) was increased reactive oxygen species (ROS), which triggered several key events (KEs) at different levels. At the cellular level, the KEs included oxidative stress, mitochondrial dysfunction, DNA damage, endoplasmic reticulum stress, reduced steroidogenic protein expression, decreased thyroid hormone synthesis, epigenetic modification process, lipid metabolism disorders, decreased androgen and estrogen receptors. These KEs led to decreased testosterone and elevated estrogen levels, alongside disruptions in spermatogenesis, oocyte maturation, and ovulation. Consequently, this resulted in lower sperm count, impaired sperm quality, and decline in oocyte quantity. Meta-analysis results showed that PFAS exposure significantly decreased juvenile survival rates (Standardized Mean Difference (SMD): -3.10, 95 % Confidence Interval (CI): -4.01, -2.18), reduced male testosterone (SMD: -4.17, 95 % CI: -6.00, -2.33) and female estradiol levels (SMD: -1.98, 95 % CI: -3.15, -0.81) in animals. Our findings systematically summarized the reproductive toxicity mechanisms of PFAS and alternatives, providing scientific basis for assessing the environmental impact.

PMID:41290085 | DOI:10.1016/j.tox.2025.154352


Enhanced-Type Quantitative Luminescence Recognition for Per- and Polyfluoroalkyl Substances (PFAS) by a Metal-Organic Framework Single Crystal - November 25, 2025

Angew Chem Int Ed Engl. 2025 Nov 24:e15775. doi: 10.1002/anie.202515775. Online ahead of print.

ABSTRACT

Rapid and quantitative detection of per- and polyfluoroalkyl substances (PFAS) remains a critical challenge in environmental monitoring due to their low light absorption capacities. Luminescent sensing based on metal-organic frameworks (MOFs) enables analyte-specific optical responses through well-defined host-guest interactions, though conventional MOF powders as sensing materials face limitations in practical deployment for their stabilities and recyclable capacities. Herein, we report a millimeter-sized luminescent MOF single crystal that functions as a reusable sensor for PFAS, exhibiting an enhanced-type luminescence response upon analyte binding. In contrast to MOF powders, which often suffer from suspension instability and material loss during recycling, the single-crystal format offers robust structural integrity, direct handling, and facile recovery. The sensor exhibits exponential luminescence responses toward five commonly encountered PFAS and retains its sensing performance for 10 cycles. This work presents a durable and scalable luminescent platform for PFAS detection and underscores the role of dimensional control in advancing MOF-based sensing technologies.

PMID:41287272 | DOI:10.1002/anie.202515775


Emerging toxicological awareness of per- and polyfluoroalkyl substances: the rising concern over 'forever chemicals' - November 25, 2025

Dis Model Mech. 2025 Nov 1;18(11):dmm052647. doi: 10.1242/dmm.052647. Epub 2025 Nov 25.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are often called 'forever chemicals'. This colloquialism reflects that many PFAS are recalcitrant to environmental and metabolic degradation, leading to long environmental and biological half-lives. This persistence, a concerning characteristic of these synthetic substances, is also a reason they are used in many products and processes. Most PFAS have physical-chemical properties that enable them to withstand extreme conditions and make them useful for a range of applications, including as surfactants or coatings that confer oil-, stain- and water-repellency. This combination of persistence and wide use has resulted in extensive environmental contamination and the presence of PFAS in living organisms, leading to use restrictions. Increasing evidence of health effects has also led to implementation of health protective guidelines. In the United States, federal regulations enacted in 2024 limit levels of six PFAS in drinking water; in the European Union, a proposed restriction would control use, import and production of the vast majority of PFAS. This Perspective article summarizes how knowledge of toxicological hazards and health-related costs of PFAS has progressed in recent years, leading to actions to restrict PFAS uses.

PMID:41288124 | DOI:10.1242/dmm.052647


Endocrine Disrupting Chemicals in Human Milk: A Systematic Review of Concentrations and Potential Health Implications - November 25, 2025

Curr Environ Health Rep. 2025 Nov 25;12(1):48. doi: 10.1007/s40572-025-00515-5.

ABSTRACT

PURPOSE OF REVIEW: Endocrine-disrupting chemicals (EDCs) disrupt the synthesis, transport, action, or metabolism of endogenous hormones in the human body. EDCs often enter the body through inhalation, ingestion, or dermal contact and can accumulate in the body. Remobilization or transfer of EDCs can occur during lactation, causing human milk to become contaminated with a variety of EDCs, which could expose nursing infants and children to these chemicals.

RECENT FINDINGS: Several studies have examined the concentration ranges for one or multiple EDC(s) in human milk. Additional studies document associations between EDC exposure and adverse health outcomes, many of which are in adult populations. It is therefore essential to understand the extent to which EDCs in human milk contribute to cumulative early-life exposures.

SUMMARY: We performed a literature review of peer-reviewed studies reporting concentrations of one or more of the following EDCs in human milk during or after 2004: bisphenols, organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), parabens, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and phthalates. We identified concentration ranges for each chemical detected in human milk and health impacts associated with early-life exposures to EDCs noted across studies from this review. Determining the presence of EDCs in human milk and the associated effects of exposure through nursing is essential to develop feeding recommendations that safeguard infant and child health.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40572-025-00515-5.

PMID:41286197 | PMC:PMC12644229 | DOI:10.1007/s40572-025-00515-5


Toxicokinetic Profiling and Developmental Toxicity of Long-Chain Per- and Polyfluoroalkyl Substances in Zebrafish - November 25, 2025

Environ Sci Technol. 2025 Nov 25. doi: 10.1021/acs.est.5c10194. Online ahead of print.

ABSTRACT

Perfluorooctanesulfonate (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnA) are three legacy long-chain per-/polyfluoroalkyl substances (PFAS). Although phased out of production, recent studies indicate substantial exposure can occur through consumption of contaminated freshwater fish, with minimal information known on the potential for developmental toxicity, especially for PFDA and PFUnA. In this study, zebrafish were used to characterize the toxicokinetics of these three PFAS as a model for developmental neurotoxicity, specifically behavior and dopamine (DA) dysregulation. Mass spectrometer quantification of water and tissue samples revealed that all three PFAS were rapidly absorbed during the early developmental window and bioconcentrated in tissue to a substantial degree. The visual motor response assay revealed altered behavioral patterns in the larvae, especially for PFDA and PFUnA. Enzyme-linked immunosorbent assay (ELISA) quantification of DA indicated these compounds induced elevations in total DA at nearly every exposure concentration for each compound down to the lowest test concentration used in this study at 0.004 ppb (ppb, μg/L) (equivalent to 4 ppb, US EPA drinking water regulation for PFOS). These findings confirm that PFOS, PFDA, and PFUnA exhibit a substantial capacity for bioaccumulation and demonstrate a need for further research into how developmental exposure impacts neurological health.

PMID:41288385 | DOI:10.1021/acs.est.5c10194


Sustainable defluorination pathway: from perfluoro gem diol hydration to electrocatalytic removal of CF<sub>3</sub> at room temperature - November 25, 2025

Phys Chem Chem Phys. 2025 Nov 25. doi: 10.1039/d5cp02881g. Online ahead of print.

ABSTRACT

At room temperature, the carbonyl functional group of some short-chain fluoroketones (SFKs) undergoes nucleophilic addition with water to form a perfluoro gem diol without protonation. This is due to the electron-withdrawing effect of their perfluoro functional group. By combining density functional theory (DFT) calculations with hydration experiments, the conditions for geminal diol formation at room temperature were determined: the Gibbs energy barrier of the transition state must not exceed 46.90 kcal mol-1, and the endergonicity associated with the formation of the target geminal diols must remain below 8.01 kcal mol-1. The strong electron-donating effect of the gem diol significantly weakens the chemical bond at the α-position. This leads to the hydrogenolysis of the CF3 group and fluorine atoms under electrocatalytic conditions, where inexpensive zinc serves as the catalyst. This eventually produces a hydrogen-substituted product without branched chains at the α position. Additionally, the alkaline environment necessary for hydrogenolysis is gradually formed during electrocatalysis with potassium fluoride (KF). The hydrogen fluoride (HF) generated during the defluorination reaction undergoes neutralization to maintain system neutrality and prevent alkaline decomposition of the perfluorinated gem diol. The entire system is in an aqueous homogeneous environment and the reaction can proceed smoothly at room temperature. This provides a more environmentally friendly and efficient approach for the synthesis of partially fluorine-substituted organic compounds at the α position, offering a potential solution for the degradation of highly fluorinated PFAS compounds in the environment.

PMID:41288513 | DOI:10.1039/d5cp02881g


A Novel Constrained Drop Surfactometer Demonstrates Inhibition of Lung Surfactant Function by PFAS Aerosols In Vitro - November 25, 2025

Abstract
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in both indoor and outdoor air, and there is increasing need to effectively screen this diverse class of chemicals for inhalation toxicity potential. Since PFAS have strong surface-active properties, we hypothesized they may interfere with lung surfactant (LS) activity. We investigated the ability of 17 PFAS delivered as liquid aerosols to inhibit LS function in a newly developed constrained drop surfactometer (CDS). Using both fluorescent tracers and mass spectrometry techniques, deposition of PFAS aerosols onto exposed LS was determined. Nine of the 17 PFAS increased surface tension (ST) above the inhibition threshold, defined as mean minimum post-exposure ST above 10 mN/m. Inhibitory compounds included legacy PFAS (perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)), emerging compounds (hexafluoropropylene oxide dimer acid, perfluoro-2-methoxyacetic acid), perfluorooctyltriethoxysilane, and perfluorooctane-sulfonamides and -sulfonamidoethanols. These compounds represent a wide range of molecular weights and functional head groups (carboxylic and sulfonic acids, sulfonamides, and siloxane). Among these compounds, the lowest modeled inhibitory doses were for N-methyl-perfluorooctane-sulfonamidoethanol (0.34 ppm) and N-ethyl-perfluorooctane-sulfonamidoethanol (0.14 ppm). Concentrations of PFOA and PFOS required to inhibit LS were significantly lower when aerosolized than when directly mixed with LS, demonstrating the importance of interactions with surfactant at the air-liquid interface. Our results show that a combination of size, functional groups, and hydrophobicity influence the ability of PFAS to inhibit LS function. Under high exposure conditions, inhaled PFAS may initiate an adverse outcome pathway through surfactant inhibition, which may ultimately produce a reduction of lung function.

Structural and Biophysical Basis for PFAS Binding by Human Sterol Carrier Protein-2 - November 24, 2025

bioRxiv [Preprint]. 2025 Oct 28:2025.10.27.684906. doi: 10.1101/2025.10.27.684906.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are harmful environmental contaminants that bioaccumulate in human tissues and are linked to adverse health outcomes. While PFAS are known to bind to a variety of lipid binding proteins (LBPs), such as human serum albumin and fatty acid-binding proteins (FABPs), the broader molecular basis for their biological distribution and breadth of protein binding in humans remains unanswered. We hypothesize that some distribution and persistence of PFAS in humans arises from a distributed network of lipid transfer proteins that collectively solubilize and transport these compounds. To support this hypothesis, we investigated the interaction between various PFAS and human sterol carrier protein 2 (SCP2), a promiscuous, structurally distinct LBP with no previously reported binding with PFAS. Using a combination of screening, fluorescence displacement assays, protein structure prediction of PFAS-SCP2 complexes, and NMR experiments, we demonstrate for the first time that SCP2 is a PFAS-binding protein. Our findings establish SCP2 as a new PFAS-interacting protein, providing insights into the residues participating in these interactions and further supporting the hypothesis that PFAS engage with a broad network of LBPs to facilitate their distribution and persistence in the human body.

PMID:41279635 | PMC:PMC12636295 | DOI:10.1101/2025.10.27.684906


Brief report on differential toxicity of legacy and second-generation PFAS on dopaminergic neurons and mitochondria - November 24, 2025

bioRxiv [Preprint]. 2025 Oct 8:2025.10.08.681169. doi: 10.1101/2025.10.08.681169.

ABSTRACT

Per/polyfluoroalkyl substances (PFAS) are anthropogenic chemicals that have shown extensive usage. Owing to widespread use and resistance to environmental degradation, they have become a hazard with respect to the environment and human health. While the legacy PFAS are being phased out, they are being replaced by second-generation PFAS that are considered safer alternatives. However, the lack of information pertaining to the underlying mechanisms for legacy and especially second-generation PFAS exacerbates the risk. This study investigates legacy and second-generation PFAS to determine their individual effects on neurotoxicity and mitochondrial respiration. Legacy PFAS, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and second-generation PFAS, GenX, and ADONA were employed, and studies were conducted using Caenorhabditis elegans and mitochondria isolated from Rat brain for Complex I to IV. It was found that legacy PFAS, PFNA, and PFDA were neurotoxic, with neurotoxicity proportional to chain length. PFOA, PFNA, and PFDA also exhibited significant inhibition to most of the mitochondrial complexes. Whereas in the case of second-generation PFAS ADONA, and GenX, it was only limited to the inhibition of Complex IV. GenX only exhibited neurodegeneration at very high doses. Our findings conclude that the legacy and second-generation PFAS might have significant neurotoxic implications. While the targets are similar to some extent, the mechanisms between the two classes are distinct. Our study the sets the stage to evaluate further the combined effect of PFAS (legacy and emergent) to fill in informational gaps pertaining to their safety.

PMID:41279863 | PMC:PMC12632472 | DOI:10.1101/2025.10.08.681169


Per- and Polyfluoroalkyl Substances (PFAS) in Sub-Antarctic Seabirds: Insights into Long-Range Transport and Bioaccumulation of Legacy and Replacement Chemicals - November 24, 2025

ACS Environ Au. 2025 Oct 3;5(6):603-615. doi: 10.1021/acsenvironau.5c00102. eCollection 2025 Nov 19.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental pollutants that can bioaccumulate in biota and cause a variety of adverse effects. Seabirds are useful bioindicators of pollutants in marine food webs because they are apex predators with broadly known diets and distributions, and concentrations in their tissues therefore reflect background exposure in particular regions and ecosystems. Concentrations of PFAS are high in seabirds in the Northern Hemisphere, but there have been few studies in the Southern Hemisphere, particularly in the sub-Antarctic, and these mostly involved a limited target list of PFAS. We detected 22 PFAS, of a target list of 39 compounds, in three species of procellariform seabirds (albatrosses and petrels) with different diets and migration strategies, sampled in two areas in the southwest Atlantic Ocean in 2004-2014. PFAS concentrations are reported for the first time in common diving petrels and white-chinned petrels. Concentrations in liver tissue varied significantly among species and years, with ΣPFAS ranging over 2 orders of magnitude from 0.08 to 7.5 ng/g (ww). Despite this variation in total concentrations, chemical contamination profiles were broadly similar, comprising mainly perfluorooctanesulfonic acid (PFOS) (∼80%) and perfluoroalkyl carboxylic acids (PFCAs) (∼15%), suggesting PFAS fingerprints are much the same despite the contrasting diets, trophic levels and distributions. This signature closely reflects mixtures found in south Atlantic waters and provides evidence of long-range transport of atmospheric precursors. Emerging compounds of concern including hexafluoropropylene oxide dimer acid (HFPO-DA), dodeceafluoro-3H-,4,8-dioxanonoate (ADONA), and short-chain perfluoroalkyl acids (PFAAs) were detected in some samples. This study provides evidence of contamination in biota and highlights the value of biomonitoring of remote environments.

PMID:41278005 | PMC:PMC12635936 | DOI:10.1021/acsenvironau.5c00102


Uncovering Exposure Patterns of Metals, PFAS, Phthalates, and PAHs and Their Combined Effect on Liver Injury Markers - November 24, 2025

J Xenobiot. 2025 Nov 1;15(6):178. doi: 10.3390/jox15060178.

ABSTRACT

People are exposed to mixtures of metals, per- and polyfluoroalkyl substances (PFAS), phthalates, and polycyclic aromatic hydrocarbons (PAH) rather than single chemicals, yet mixture inference is hampered by high dimensionality, correlation, missingness, and left-censoring below limits of detection (LOD). We analyzed 2013-2014 National Health and Nutrition Examination Survey (NHANES) biomarkers (n = 4367) to (i) recover latent, interpretable co-exposure structures and (ii) quantify how these mixtures relate to liver health. To denoise and handle censoring, we applied Principal Component Pursuit with LOD adjustment (PCP-LOD), decomposing the exposure matrix into a non-negative low-rank component (population co-exposure profiles) and a sparse component (individual spikes), and then used Bayesian Kernel Machine Regression (BKMR) to estimate nonlinear and interactive associations with AST, ALT, GGT, ALP, total bilirubin, and the Fatty Liver Index (FLI), retaining analytes with ≥50% detection. PCP-LOD revealed coherent clusters (e.g., long-chain PFAS grouping; shared metal loadings), while the sparse layer highlighted episodic phthalate elevations. BKMR indicated outcome-specific mixture effects: PAHs and selected phthalates showed consistently positive associations with ALP, GGT, and FLI; PFAS (PFOS, PFNA, PFOA) exhibited modest associations with ALP and bilirubin; metals displayed mixed directions. A joint increase in the overall mixture from the 25th to 75th percentile corresponded to an upward shift in FLI and a smaller rise in ALT. This censoring-aware low-rank-plus-sparse framework coupled with flexible mixture modeling recovers actionable exposure architecture and reveals clinically relevant links to liver injury and steatosis, motivating longitudinal and mechanistic studies to strengthen causal interpretation.

PMID:41283416 | PMC:PMC12641841 | DOI:10.3390/jox15060178


Comprehensive Screening of Per- and Polyfluoroalkyl Substances in Cosmetics and Personal Care Products: Implications for Human Dermal Exposure Risk - November 24, 2025

Environ Sci Technol. 2025 Nov 23. doi: 10.1021/acs.est.5c11490. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) in beauty products pose a potential human exposure risk through dermal contact. To better understand the potential exposure risk, PFAS were analyzed in 64 beauty products. Target analysis indicated that long-chain perfluoroalkyl carboxylic acids (C8-C9 PFCAs) appeared at high detection frequencies but low levels across all products, while C4-C7 PFCAs were detected at high levels in the products labeled with fluorinated ingredients (F-listed products). Total oxidizable precursor assay revealed widespread presence of perfluoroalkyl acid precursors in 95% of the samples, with levels in three of the F-listed products reaching nearly 1000 times the ∑targetPFCAs. Suspect and nontarget analysis based on high-resolution mass spectrometry identified 20 emerging PFAS, including ultrashort-chain, ether-containing, fluorotelomer- and perfluoroalkyl sulfonamide-derived PFAS. Semiquantification using structurally similar standards showed that the ∑emergingPFAS level ranged from 1.26 ng/g to 6.54 μg/g, with higher concentrations in the F-listed products. It is predicted that transdermal absorption via using F-listed cosmetics serves as the second most significant PFAS exposure route in the general population, with the median estimated ∑PFAS exposure level (1.28 ng/kg bw/day) exceeding the EFSA's recommended threshold. Our findings underscore that fluorinated ingredients in beauty products may introduce high levels of PFAS and pose a potential exposure risk, warranting further attention.

PMID:41276955 | DOI:10.1021/acs.est.5c11490


Machine Learning-Driven Cross-Species Toxicity Prediction for Advancing Ecologically Relevant PFAS Water Quality Criteria - November 24, 2025

Environ Sci Technol. 2025 Nov 24. doi: 10.1021/acs.est.5c12013. Online ahead of print.

ABSTRACT

Traditional toxicity testing cannot keep pace with the rapid growth of synthetic chemicals, creating major data gaps that hinder the development of water quality criteria (WQC) for emerging contaminants. This study developed a machine learning model integrating compound- and organism-related features to enable cross-compound and cross-species toxicity prediction. The model demonstrated strong robustness and generalization, outperforming the Interspecies Correlation Estimation application in cross-species prediction, particularly across large taxonomic distances. SHAP analysis identified water solubility and lipophilicity as dominant predictors, with organism-related features also contributing substantially. The model predicted the acute toxicity of 30 representative per- and polyfluoroalkyl substances (PFAS) across 181 aquatic species. Habitat-informed species selection was then used to derive ecologically relevant 5% hazardous concentrations (HC5), which were generally higher in saltwater than in freshwater. Cross-regional comparisons further indicated that salinity may modulate fish sensitivity to PFAS. HC5 estimates for China were higher than those for North America and Europe, potentially reflecting inter-regional differences in species sensitivity, with Chinese species appearing comparatively more tolerant. Finally, site-specific WQC for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were derived for the Great Lakes using predicted sensitivities of 76 dominant native species, providing greater ecological relevance than existing criteria.

PMID:41284935 | DOI:10.1021/acs.est.5c12013


HRMS-Based Suspect and Nontarget Screening for Comprehensive PFAS Analysis of Soils near a Fluorochemical Site in Flanders - November 24, 2025

Environ Sci Technol. 2025 Nov 24. doi: 10.1021/acs.est.5c13206. Online ahead of print.

ABSTRACT

Targeted analysis of per- and polyfluoroalkyl substances (PFAS) relies on a limited number of reference standards, and consequently, many PFAS remain unidentified, which restricts comprehensive monitoring and risk assessment. Here, we apply high-resolution mass spectrometry (HRMS)-based suspect and nontarget screening (SS/NTS), alongside targeted analysis, to detect and (semi)quantify legacy, emerging, and novel PFAS in soils near a PFAS hotspot in Flanders, Belgium. Targeted analysis quantified 36 PFAS, with perfluorooctanesulfonic acid (PFOS) as the most predominant, alongside precursors such as ethyl perfluorooctane sulfonamido acetic acid (Et-FOSAA) and perfluorooctane sulfonamide (FOSA). On the other hand, SS/NTS identified over 100 PFAS homologues and isomers, including pentafluorosulfide sulfonic acids (SF5-PFSAs), perfluorophosphinic acids (PFPiAs), and perfluorophosphoric diesters (PFPDEs). Total PFAS concentrations at the 3M site varied widely, reaching 118.5 μg/g, among the highest reported globally. These findings highlight the complexity of PFAS contamination in the study area and the need for site-specific analyses to support monitoring, source tracking, regulation, and risk assessment.

PMID:41284757 | DOI:10.1021/acs.est.5c13206


Organics-to-energy revolution: NALG's hybrid solution tackles FOGO & PFAS - November 24, 2025

The essence of NALG's integrated approach lies in fostering a circular economy where the right technologies are adapted to effectively convert organic ...


Associations of per- and polyfluoroalkyl substances exposure with kidney function in the Korean general population - November 23, 2025

Ecotoxicol Environ Saf. 2025 Nov 22;307:119462. doi: 10.1016/j.ecoenv.2025.119462. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are persistent and harmful environmental pollutants of international concerns. Despite widespread use of PFAS in industrial and consumer products, research exploring their effects on kidney function among Asian populations remains limited. Therefore, this study analyzed the Korean National Environmental Health Survey cycle 4 (2018-2020) data to determine the relationship between renal function and serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDeA) using the estimated glomerular filtration rate (eGFR). Subjects with eGFR values less than 60 mL/min/1.73 m2 were classified as having chronic kidney disease (CKD). Multiple linear and logistic regression models were used to assess the associations between PFAS concentrations and eGFR, and Bayesian kernel machine regression was used to evaluate the combined effects of PFAS on renal function. Among the general Korean adult population (n = 2985) significant negative associations were observed between all PFAS and the eGFR (p < 0.001). Natural log transformed level of PFOA, PFOS, PFHxS, PFNA, and PFDeA were associated with odds ratios of 1.801 (95 % confidence interval [CI]: 1.010-3.213), 1.961 (95 % CI: 1.407-2.732), 1.545 (95 % CI: 1.178-2.026), 2.334 (95 % CI: 1.424-3.825), and 1.782 (95 % CI: 0.976-3.254), respectively. Additionally, eGFR was significantly reduced as all PFAS concentrations simultaneously increased, and this association was mainly driven by PFNA and PFDeA. These associations remained consistent after stratification by sex and age. These findings suggest that PFAS exposure is associated with CKD and may have adverse effects on kidney function.

PMID:41275640 | DOI:10.1016/j.ecoenv.2025.119462


Exposure to per- and polyfluoroalkyl substances (PFAS) and phthalate metabolites and their association with low estimated glomerular filtration rates in the US population - November 23, 2025

Food Chem Toxicol. 2025 Nov 21;207:115853. doi: 10.1016/j.fct.2025.115853. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in consumer products and polymers. Human exposure occurs through multiple pathways and has been linked to renal, neurologic, and endocrine toxicities. This study examined associations between PFAS and phthalate metabolites and reduced kidney function, as measured by estimated glomerular filtration rate (eGFR), using National Health and Nutrition Examination Survey (NHANES) 2013-2018 data. Participants who were non-Hispanic Black, over 40 years, or with serious heart disease showed higher likelihood of low eGFR. Among PFAS, exposure to MPAH was significantly associated with low eGFR (odds ratio [OR] 2.85; 95 % confidence interval [CI]: 1.31-6.21). Multiple phthalate metabolites were also positively associated with low eGFR, including MCOP, MCNP, MECPP, MBP, MEP, MEHHP, MHNCH, MEHP, MiBP, MEOHP, and MBzP, with ORs ranging from 1.42 to 2.50 across models. These findings suggest both PFAS and phthalate exposures are linked to kidney dysfunction in U.S. adults, with particularly strong associations for several phthalate metabolites. The results highlight the potential nephrotoxic risks of widespread chemical exposures and underscore the need for further studies on cumulative effects and vulnerable subpopulations.

PMID:41275905 | DOI:10.1016/j.fct.2025.115853


Highly Selective Adsorption of Fluorinated Gases by Porous Organic Cages - Effects of Fluorinated Side-Chains - November 22, 2025

Adv Mater. 2025 Nov 21:e16358. doi: 10.1002/adma.202516358. Online ahead of print.

ABSTRACT

Perfluorocarbons (PFCs) as well as related gases such as sulfur hexafluoride (SF6) or nitrogen trifluoride (NF3) are examples of F-gases, a subclass of per- and polyfluoroalkyl substances (PFAS). F-gases are anthropogenic greenhouse gases with the highest global warming potentials known and thus contribute significantly to global warming. To reduce their amount in the atmosphere, selectively adsorbing materials would be beneficial, but such materials are rare. A homologous series of porous organic cages with fluorinated side-chains is synthesized and depending on the targeted gas as well as operating temperature, different cages have high selectivities for certain F-gases against N2, CO2, and O2. Within this series, new benchmark selectivities against, e.g., perfluoro propane (PFC-218) and perfluoro cyclobutane (PFC-318) have been achieved based on attractive fluorine-fluorine interactions. Furthermore, these interactions are exploited for the first time in the adsorption of sulfur hexafluoride and nitrogen trifluoride.

PMID:41272994 | DOI:10.1002/adma.202516358


Mass spectrometry imaging unveils intergenerational toxicity of a novel PFECA (C7 HFPO-TA) in zebrafish - November 22, 2025

J Hazard Mater. 2025 Nov 19;500:140540. doi: 10.1016/j.jhazmat.2025.140540. Online ahead of print.

ABSTRACT

2-[2-(Trifluoromethoxy)hexafluoropropoxy]tetrafluoropropanoic acid (C7 HFPO-TA), a novel perfluoropolyether carboxylic acid (PFECA) identified as a high-priority emerging PFAS in Taihu Lake (447 µg/L), has been widely adopted as a PFOA substitute. However, its ecotoxicological effects, particularly long-term exposure-mediated multigenerational toxicity in aquatic organisms, remain unknown. In this study, we systematically evaluated the multigenerational toxicity of C7 HFPO-TA in zebrafish at an environmentally relevant concentration (500 µg/L). Maternal exposure induced significant offspring malformations (p < 0.05), predominantly pericardial edema (41.32 % incidence) and spinal curvature (17.67 %). By airflow-assisted ionization mass spectrometry imaging (AFAI-MSI), we demonstrated for the first time that C7 HFPO-TA may undergo transovarian transfer and induce tissue-specific metabolic perturbations. C7 HFPO-TA accumulation in oocytes triggered severe downregulation of arachidonic acid (AA) and glycerophospholipid metabolites (p < 0.001) in larval spinal tissue, which could disrupt skeletal development. Suppressed purine and folate metabolism (p < 0.001) in pericardial regions correlated with oxidative stress, potentially impairing cardiac function. Notably, the metabolic disruptions persisted in F1 offspring despite reduced chemical burden. Our study integrates spatial pollutant imaging with spatial metabolomics, advancing mechanistic toxicity assessment for emerging PFAS. The findings underscore that C7 HFPO-TA may not be a safe PFOA alternative due to its transgenerational risks, urging stricter regulation of PFECAs in aquatic ecosystems.

PMID:41273971 | DOI:10.1016/j.jhazmat.2025.140540


Prenatal exposure to per- and polyfluoroalkyl substances and neurodevelopment trajectory: towards early warning via cohort- and metabolomics-based risk ranking - November 22, 2025

BMJ Ment Health. 2025 Nov 21;28(1):e301912. doi: 10.1136/bmjment-2025-301912.

ABSTRACT

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely affect neurodevelopment, but comparative risks and metabolic disruptions remain unclear.

OBJECTIVE: To integrate various levels of evidence and illustrate the relationship between prenatal PFAS exposure and neurodevelopmental trajectories in children.

METHODS: In the Shanghai-Minhang birth cohort, maternal PFAS were measured from plasma collected at 12-16 weeks' gestation. Neurodevelopment was assessed at 6, 12 and 48 months using the Ages and Stages Questionnaire-3 and group-based trajectory modelling was performed. Associations between PFAS (co-)exposure and neurodevelopment were evaluated using logistic regression and mixture model effects. Metabolomic perturbations of PFAS with potential neurodevelopmental effects were analysed in PC12 neuronal cells.

FINDINGS: Among 412 mother-child pairs, higher PFAS exposure was linked to suboptimal development in communication (highest vs lowest tertile: ORPFHxS=2.96, 95% CI 1.05 to 8.35, ptrend=0.064; ORPFOS=3.45, 95% CI 1.27 to 9.43, ptrend=0.012), personal-social (highest vs lowest tertile: ORPFNA=2.41, 95% CI 1.05 to 5.56, ptrend=0.036), and total score (highest vs lowest tertile: ORPFOS=2.32, 95% CI 1.09 to 4.91, ptrend=0.028) across early childhood. Metabolomic analysis revealed disrupted excitatory/inhibitory (E/I) neurotransmission. Integrated toxicological assessment, including exposure risk information, toxicogenomic signatures, bioassay-inferred toxicity and in vitro neurotoxicity profiles, ranked PFOS as the most neurotoxic, followed by perfluorooctanoic acid, perfluorohexanoic acid, perfluorohexanesulfonic acid and 6:2 chlorinated polyfluorinated ether sulfonate. An E/I imbalance-based screening identified 8.3% of children as high-risk for PFAS-related neurodevelopmental deficits.

CONCLUSIONS: Prenatal PFAS exposure is associated with suboptimal neurodevelopment, particularly in communication and social interaction.

CLINICAL IMPLICATIONS: Maternal exposure profiles during early gestation that are associated with disrupted E/I neurotransmission may serve as early indicators of increased risk for suboptimal neurodevelopment, thereby informing timely preventive interventions.

PMID:41274667 | DOI:10.1136/bmjment-2025-301912


Nov. 21 Policy Watch: Vaccine-autism link 'not ruled out,' CDC says - C&EN - November 21, 2025

In other news, Georgia aligns its proposed PFAS drinking-water limits with the USEPA, and the European Union considers adding melamine to its ...


Next Generation Risk Assessment of Emerging PFOA Alternatives Using Integrated New Approach Methodologies - November 21, 2025

Environ Sci Technol. 2025 Nov 21. doi: 10.1021/acs.est.5c11122. Online ahead of print.

ABSTRACT

The global restriction of legacy per- and polyfluoroalkyl substances (PFASs), such as perfluorooctanoic acid (PFOA), has led to increased production and environmental occurrence of emerging alternatives. This study applied a next generation risk assessment (NGRA) framework to evaluate and compare the local environmental risks of eight PFOA alternatives using multiple lines of evidence from new approach methodologies (NAMs). Targeted chemical analysis was conducted to quantify environmental concentrations in wastewater and surface waters near an industrial source. Hazard characterization integrated in silico modeling, in vitro assays using zebrafish liver cells, in vivo zebrafish embryo toxicity tests, and transcriptomic profiling. Multiple points of departure (PODs), including conventional effect concentrations, benchmark concentrations (BMC), transcriptomic POD (tPOD), and species sensitivity distributions (SSD), were derived. The results showed that HFPO-TA and HFPO-TeA were cytotoxic, while HFPO-DA, HFPO-TA, and HFPO-TeA caused significant embryo toxicity. HFPO-TeA emerged as the most potent alternative, with transcriptomic signatures implicating disruption of metabolic and cardiovascular functions. Risk quotients (RQ) for HFPO-DA exceeded concern thresholds across end points, while those for HFPO-TA and HFPO-TeA declined with appropriate assessment factor adjustments. These findings highlight potential local environmental risks from PFOA alternatives and demonstrate the utility of NAM-based NGRA frameworks.

PMID:41270243 | DOI:10.1021/acs.est.5c11122


Novel insights from multivariate analysis of metadata from a large PFAS remedial investigation dataset - November 21, 2025

J Hazard Mater. 2025 Nov 19;500:140539. doi: 10.1016/j.jhazmat.2025.140539. Online ahead of print.

ABSTRACT

The extensive use of per- and polyfluoroalkyl substances (PFAS) in aqueous film-forming foam (AFFF) has resulted in widespread environmental contamination. This study applies Principal Component Analysis (PCA) and Hierarchical Clustering Analysis (HCA) to approximately 21,000 PFAS records collected from 29 sites in the continental United States to identify compositional patterns, source signatures, and spatial trends across groundwater, porewater, surface water, soil, and sediment at AFFF source areas and downgradient plumes . A novel concept termed the estimated PFAS vadose zone dilution attenuation factor (the ratio between PFAS porewater and groundwater concentration) is defined herein and negatively correlated with perfluorinated chain length, reflecting sorption and mobility differences. PCA revealed clustering by chain length and media type: short-chain PFAS dominated aqueous samples, while long-chain PFAS were prevalent in soil and sediment. PFHxS was most abundant in groundwater and porewater; PFOS dominated surface water and solids. The maximum PFAS soil concentrations are generally limited to the upper 1 m in arid climates and deeper in sub-humid regions. Site-specific PFAS fingerprints were associated with hydroclimatic variables. PCA results suggest diffuse contamination patterns, likely due to historical AFFF application. These findings support refinement of the site-specific knowledge framework, inform risk assessments, and guide targeted sampling and remediation strategies at PFAS-impacted sites.

PMID:41270413 | DOI:10.1016/j.jhazmat.2025.140539


Deciphering the toxicological mechanisms of per- and polyfluoroalkyl substances (PFAS) in musculoskeletal disorders via integrated network toxicology and molecular docking - November 21, 2025

Environ Int. 2025 Nov 19;206:109934. doi: 10.1016/j.envint.2025.109934. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) have been extensively used in everyday products; however, their effects on human health remain largely unknown. This study aimed to investigate the potential mechanisms by which PFAS may contribute to functional disorders in the human musculoskeletal system. Four representative musculoskeletal disorders were selected, which included intervertebral disc degeneration, myositis, osteoarthritis, and osteoporosis. Advanced network toxicology approaches integrating data from the Comparative Toxicogenomics Database (CTD) and GeneCards identified potential PFAS-associated targets for each disorder. Molecular docking simulations were employed to assess interactions between PFAS and target proteins. Molecular docking of a series of PFAS molecules against multiple protein targets revealed strong binding affinities. Prioritization based on average binding energies highlighted the targets with the greatest PFAS-binding potential. A subsequent comprehensive analysis further discussed these findings by integrating the functional roles of the targets and the classification of the various PFAS compounds. Evidence synthesis confirmed that these core targets are critically involved in key pathological processes common to musculoskeletal diseases, including chronic inflammation, oxidative stress, apoptosis, extracellular matrix degradation, and impaired bone remodeling. This study provides innovative insights into the mechanisms by which environmental pollutants contribute to human diseases, thereby establishing a theoretical foundation for disease prevention and therapeutic strategies.

PMID:41270661 | DOI:10.1016/j.envint.2025.109934


Identification of a PFAS hyperaccumulator and elucidation of its translocation mechanism for sustainable phytoremediation - November 21, 2025

Nat Commun. 2025 Nov 21;16(1):10283. doi: 10.1038/s41467-025-65191-3.

ABSTRACT

Remediation of soils contaminated by the globally concerning per- and polyfluoroalkyl substances (PFAS) is imperative yet challenging. Herein, we identify a PFAS hyperaccumulator, the herbaceous Oenothera rosea, in soil near a fluorochemical facility and demonstrate root-to-shoot translocation factors of 3.07 - 58.6 for 18 distinct PFAS. Comparative hydroponic/pot experiments using conspecifics from non-polluted areas confirm that hyperaccumulation arises from domestication after prolonged PFAS exposure. Root cell wall pectin and hemicellulose are critical PFAS binding sites, significantly affecting root-to-shoot translocation. Subcellular and transcriptomic analyses reveal that the hyperaccumulating O. rosea undergoes minimal cell wall remodeling under PFAS stress, a signature of adaptive evolution. Life cycle assessment further validates the environmental superiority of an integrated strategy combining O. rosea phytoremediation with biomass pyrolysis for PFAS destruction and biochar production, achieving a net-negative carbon footprint (-17.9 kg CO2/ton soil). Our work provides a comprehensive framework for PFAS remediation, from hyperaccumulator identification to sustainable field application.

PMID:41271697 | PMC:PMC12638775 | DOI:10.1038/s41467-025-65191-3


The carcinogenic mechanism of per- and polyfluoroalkyl substances on clear cell renal cell carcinoma: a combined study of network toxicology and virtual drug screening - November 21, 2025

Int J Environ Health Res. 2025 Nov 21:1-14. doi: 10.1080/09603123.2025.2587842. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) have been implicated in various adverse health effects, but their association with clear cell renal cell carcinoma (ccRCC) - a prevalent and aggressive form of kidney cancer often diagnosed at advanced stages - remains unclear. This study employs an integrative computational approach combining network toxicology, machine learning-based prognostic modeling, and virtual drug screening to elucidate the potential mechanistic links between PFAS exposure and ccRCC pathogenesis. Network toxicology analysis identified critical intersection genes, while machine learning evaluation of The Cancer Genome Atlas (TCGA) database revealed key prognostic biomarkers. Furthermore, virtual screening identified several promising therapeutic candidates, including Ecteinascidin, Avodart, and Nilotinib, which demonstrated high binding affinity to pivotal molecular targets such as AIM2, HK3, ATP1A1, and ZAP70. Our findings suggest a potential link/role of PFAS in ccRCC development via dysregulation of specific gene pathways, and the identified compounds could serve as potential therapeutic agents. This study provides novel insights into the carcinogenic mechanisms of PFAS in ccRCC and proposes new avenues for targeted therapy. However, further experimental and clinical validation is necessary to confirm these findings and translate them into improved patient outcomes, while also addressing broader environmental health concerns related to PFAS exposure.

PMID:41269153 | DOI:10.1080/09603123.2025.2587842


Perfluorooctane sulfonate (PFOS) adsorption on Fe-rich mineral assemblages and soils: experiments and surface complexation modeling - November 21, 2025

Geochem Trans. 2025 Nov 21;26(1):9. doi: 10.1186/s12932-025-00105-2.

ABSTRACT

Perfluorooctane sulfonate (PFOS) is an emerging contaminant frequently detected in subsurface environments, raising significant concern due to its environmental persistence, mobility, and potential human health impacts. This study examines PFOS adsorption onto a range of solid substrates, including pure minerals, mineral assemblages, and natural soils. Specifically, the adsorption behavior of 2-line ferrihydrite, ferrihydrite-coated sand, and soil collected from a PFOS-impacted site in Killingworth, Connecticut was investigated to evaluate their capacity to retain PFOS under varying geochemical conditions. By integrating batch adsorption experiments with surface complexation modeling (SCM) and applying the component additivity approach, this study elucidates the reactive transport mechanisms governing PFOS behavior under a range of geochemical conditions. Our findings demonstrate that PFOS adsorption occurs significantly on both ferrihydrite and quartz surfaces, with the ferrihydrite-coated sand and soil exhibiting retention behavior attributable to contributions from both mineral phases. At lower pH values, sorption is predominantly governed by outer-sphere complexation driven by the surface charge characteristics of ferrihydrite. Specifically, under acidic conditions (pH < 5.5 for ferrihydrite-coated sand and pH < 6.0 for soil), PFOS retention is primarily facilitated through an outer-sphere hydrogen-bonded complex at ferrihydrite's surface, while a secondary outer-sphere complex involving Na+ co-adsorption contributes to a lesser extent. At elevated pH levels, however, electrostatic interactions become less favorable, and non-electrostatic hydrophobic interactions with quartz surfaces become increasingly dominant, highlighting the transition in sorption mechanisms from charge-driven to hydrophobic partitioning under neutral to alkaline conditions. A comparison with traditional partitioning coefficients (Kd) revealed that their variability closely corresponds with changes in dominant surface complexes across different pH conditions. Given the critical role of solid-phase partitioning in governing PFAS transport in the subsurface, enhanced predictive capabilities are essential for advancing site-specific risk assessments and informing management strategies aimed at protecting both public and private water resources.

PMID:41269454 | PMC:PMC12639654 | DOI:10.1186/s12932-025-00105-2


Reference values of per- and poly- fluoroalkyl substances concentration in serum and related factors in Korean adults: Korean National Environmental Health Survey - November 20, 2025

Environ Anal Health Toxicol. 2025 Sep;40(3):e2025021-0. doi: 10.5620/eaht.2025021. Epub 2025 Sep 17.

ABSTRACT

This study determined reference values of per- and polyfluoroalkyl substance (PFAS) exposure in the general Korean population. Serum samples from 2,993 adults in the fourth Korean National Environmental Health Survey (KoNEHS) (2018 -2020) were analyzed for five PFAS: perfluorooctanoic acids (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA). The geometric means (GMs) and 95th percentile concentrations of serum PFOA were 6.43 and 16.55 μg/L, respectively; those of PFOS were 15.07 and 43.96 μg/L; 4.17 and 14.91 μg/L for PFHxS; 2.06 and 5.98 μg/L for PFNA; and 0.91 and 2.40 μg/L for PFDA. Higher serum PFAS concentrations were observed in older adults, men, former smokers, and frequent seafood consumers. Exposure levels also varied based on socioeconomic factors such as income and education. Additionally, participants residing in coastal areas exhibited higher serum PFAS concentrations, whereas higher PFHxS levels were observed in those living near industrial complexes. Higher concentrations of PFDA and PFNA were detected in participants consuming local drinking water (GMs, 3.29, 2.86 and 2.82 μg/L for local-based water, tap water and purifier or mineral water for PFNA; 1.43, 1.22 and 1.20 μg/L for PFDA; p-values were <0.05). These findings suggest that the Korean PFAS exposure level is relatively high, and may be related with residential and lifestyle characteristics.

PMID:41265405 | DOI:10.5620/eaht.2025021


Life Cycle Assessment and Life Cycle Costing Analysis for Removing Per- and Polyfluoroalkyl Substances from Landfill Leachate with Foam Fractionation Technology - November 20, 2025

ACS ES T Water. 2025 Oct 22;5(11):6289-6298. doi: 10.1021/acsestwater.5c00381. eCollection 2025 Nov 14.

ABSTRACT

Understanding the environmental impacts and economic costs of treatment technologies is essential for developing sustainable strategies for managing per- and polyfluoroalkyl substances (PFASs). This study focuses on the treatment of PFAS-contaminated landfill leachate using foam fractionation (FF) technology. A parametrized life cycle assessment and life cycle costing analysis were conducted to evaluate the performance of one-stage and three-stage FF systems. Full-scale operational data and EPA design models were used to assess environmental and economic impacts based on a functional unit of treating 1000 m3 of PFAS-contaminated landfill leachate. The global warming potential was estimated at 818 kg CO2 eq for the one-stage system with 20% foam fraction, 357 kg CO2 eq for the one-stage system with 1% foam fraction, and 402 kg CO2 eq for the three-stage system with 1% foam fraction. Life cycle costs were estimated at $77.4 and $110.6 per functional unit for the one-stage and three-stage systems, respectively, using the net present value method. Sensitivity and scale-up analyses were also performed to evaluate the influence of operational parameters and system configurations on both environmental and economic outcomes.

PMID:41262143 | PMC:PMC12624725 | DOI:10.1021/acsestwater.5c00381


Correlation between metabolite concentrations in the frontal lobes, determined using <sup>1</sup>H-MRS, and IQ in children with foetal alcohol spectrum disorder - November 20, 2025

Pol J Radiol. 2025 Oct 3;90:e484-e489. doi: 10.5114/pjr/208024. eCollection 2025.

ABSTRACT

PURPOSE: Foetal alcohol spectrum disorder (FASD) is a broad term describing a range of conditions that may be caused by prenatal exposure to alcohol. The aim of this study is to assess the relationship between the metabolism in the frontal lobes of the brain and the IQ in children with FASD.

MATERIAL AND METHODS: The study assessed a total of 124 children of both genders, aged 5-17 years, with diagnosed FASD, including 62 children with foetal alcohol syndrome (FAS), 34 children with partial foetal alcohol syndrome (pFAS), and 28 children with alcohol-related neurodevelopmental disorder (ARND). The Wechsler Intelligence Scale for Children (WISC-R) and proton magnetic resonance spectroscopy (1H-MRS) in frontal lobes were performed.

RESULTS: There was a statistically significant difference in IQ scores between the group of children with FASD (mean 90.42) and the control group (mean 121.26). In 1H-MRS, significantly higher Lip/Cr levels were observed in the children with FASD than in the controls in the left frontal lobe. There is a significant negative correlation between IQ scores and Lip/Cr concentrations in the right frontal lobe and in both frontal lobes in children with FASD.

CONCLUSIONS: Children with FASD have a significantly lower IQ than their peers from a healthy control group. This may be linked to the changes in the frontal lobes caused by prenatal alcohol consumption, in particular the elevated lipid levels.

PMID:41262500 | PMC:PMC12624464 | DOI:10.5114/pjr/208024


Adsorptive Removal of PFAS from Aqueous Solutions Using GAC, PAC and Ball-Milled Colloidal Activated Carbon: Characterizing Efficiency, Kinetics, and Mechanisms - November 20, 2025

ACS ES T Water. 2025 Nov 3;5(11):6554-6566. doi: 10.1021/acsestwater.5c00641. eCollection 2025 Nov 14.

ABSTRACT

Per-and polyfluoroalkyl substances (PFAS) present significant challenges for remediation due to their persistence in nature. Activated carbon is a widely used adsorbent for removing PFAS. In this study, three forms of activated carbon, granular activated carbon (GAC), powdered activated carbon (PAC), and ball-milled colloidal activated carbon (CACBM), are compared for their effectiveness in removing short and long-chain PFAS. Physical modification through ball-milling process enhanced the adsorptive properties of activated carbon, resulting in smaller particle size (d 50 = 0.318 μm), increased surface area (968.59 m2 g-1), and improved suspension stability compared to conventional GAC and PAC. Kinetic experiments showed that CACBM demonstrated superior removal efficiencies of long-chain PFAS (up to 89% for perfluorooctanesulfonic acid (PFOS) and 73% for perfluorooctanoic acid (PFOA)), and moderate removal of short-chain PFAS (55% for perfluorobutanesulfonic acid (PFBS) and 30% for perfluorobutanoic acid (PFBA)). The pseudo-first-order model adequately described adsorption trends; however, the pseudo-second-order model provided a better fit, with intraparticle diffusion identified as the rate-limiting step. Isotherm studies indicated that PFAS adsorption aligned well with the Freundlich model. Competitive adsorption experiments revealed a hierarchical pattern. Overall, the study demonstrates CACBM as a promising adsorbent for remediation of PFAS-contaminated water systems.

PMID:41262144 | PMC:PMC12624724 | DOI:10.1021/acsestwater.5c00641


A novel method for assessing chemical leaching from surface water-pavement interactions applied to recycled-tyre reuse products - November 20, 2025

Environ Sci Process Impacts. 2025 Nov 20. doi: 10.1039/d5em00516g. Online ahead of print.

ABSTRACT

Globally, recycling of otherwise waste materials into new products is desired. End-of-life tyres are increasingly incorporated into new pavement materials but leaching of entrained chemicals from such products is not well quantified. Chemical concentrations in runoff from pavements may pose environmental and human health risks. High liquid-solid ratio, batch-agitated leaching is standard practice for assessing leachability and hazards of chemicals-of-potential-concern in contaminated soil and wastes but is not reflective of important exposure scenarios and may mislead. A new static surface leaching procedure (SSLP) is introduced that is more representative of chemical leaching from pavement reuse materials whilst in contact with rainfall/runoff water. SSLP was evaluated over 2-14 d intervals against batch-agitated leaching for two rubberised pavement products containing 10-fold different proportions of crumbed end-of-life tyres. Although, batch leaching showed high mass removal of 1,3-diphenylguanidine (1,3-DPG, 34%) and hexamethoxymethylmelamine (HMMM, 30%), both batch- and SSLP-leached concentrations of 1,3-DPG, HMMM and N1-(4-methylpentan-2-yl)-N4-phenylbenzene-1,4-diamine quinone (6PPD-Q) were below ECOSAR-predicted toxicity thresholds for fish and daphnids. SSLP highlighted differences in chemical leachability based on rubber content of pavement products and offers a method applicable to other scenarios, such as PFAS leaching from concrete/asphalt pavements. The SSLP was shown to approximate one-dimensional leaching from the surface of the pavement and to be dominated by diffusive processes, thus yielding a simple repeatable approach.

PMID:41263588 | DOI:10.1039/d5em00516g


Paternal Folic Acid Supplementation Alleviated Hepatic Steatosis in Male Offspring Through Sperm DNA Methylation Modification - November 20, 2025

Mol Nutr Food Res. 2025 Nov 20:e70328. doi: 10.1002/mnfr.70328. Online ahead of print.

ABSTRACT

In recent years, studies have demonstrated a link between paternal preconception nutrient exposure and the phenotype of the offspring. However, there is a paucity of direct scientific evidence on the effects and the underlying mechanism of paternal folic acid supplementation (PFAS) on offspring phenotype. In this study, male mice were fed different doses of folic acid for 10 weeks, and then mated with females to produce offspring. In our findings, male offspring of PFAS fathers exhibit lower body weight and reduced hepatic lipid accumulation. Moreover, liver lipidomics analysis indicates the beneficial effect of PFAS on offspring hepatic lipid homeostasis. Offspring of PFAS exhibited altered gene expression patterns in the liver, with downregulation of several genes involved in lipid metabolism and inflammation signaling pathways. Mechanistically, whole genome bisulfite sequencing (WGBS) of paternal sperm revealed changes in gene expression of offspring liver depending on PFAS, including reproducibly increased methylation at the intron region of Acc1 and the promoter region of Scd1, the key gene of lipid metabolism, in the liver of PFAS offspring. However, these epigenetic findings are exploratory and require confirmation with a larger sample size. Overall, this study provides the first evidence of beneficial effect of paternal folic acid administration on preventing NAFLD in the offspring.

PMID:41263017 | DOI:10.1002/mnfr.70328


From Home to Hazard: Tracking PFAS From Residential Wastewater Through Wastewater Treatment Sludge to Sludge-Derived Ash - November 20, 2025

Water Environ Res. 2025 Nov;97(11):e70214. doi: 10.1002/wer.70214.

ABSTRACT

Poly- and perfluoroalkyl substances (PFAS), commonly known as "forever chemicals," are highly persistent environmental contaminants widely present in municipal wastewater due to their extensive use in consumer products and industrial applications. This study quantitatively tracks PFAS occurrence, transformation, and fate across three municipal wastewater treatment plants (WWTPs A, B, and C; design capacities: 3, 0.8, and 13 MGD). Composite sampling revealed that influent ∑PFAS ranged from 186 to 365 ng/L, while effluent ∑PFAS ranged from 247 to 361 ng/L, reflecting increases of 4%-23% attributable to precursor transformation during treatment. For grab samples, influent ∑PFAS spanned 157-234 ng/L, with effluent values of 189-322 ng/L, representing site-specific variation from -13% to +25%. The total oxidizable precursor (TOP) assay results indicated substantially higher ∑PFAS due to precursor oxidation: influent values increased to 424-882 ng/L (2.1-3 times higher than target analysis) and effluent rose to 565-901 ng/L (up to 4 times higher). Sludge samples contained ∑PFAS of 3282-5324 ng/kg, an order of magnitude above aqueous samples and dominated by short-chain PFCAs (70%-85%). However, incineration demonstrated an approximate 99% reduction in PFAS content in sludge-derived ash, confirming its potential as an effective destruction method. The results thus emphasize WWTPs as secondary sources of PFAS contamination and the critical need for enhanced regulatory monitoring and advanced treatment strategies to mitigate their environmental and public health risks.

PMID:41263701 | DOI:10.1002/wer.70214


Bacterial cellulose for emerging contaminants: A review of applications for PFAS, nanoplastics, and endocrine disruptors in water treatment - November 20, 2025

Sci Total Environ. 2025 Nov 19;1008:180976. doi: 10.1016/j.scitotenv.2025.180976. Online ahead of print.

ABSTRACT

Emerging contaminants, including per- and polyfluoroalkyl substances (PFAS), nanoplastics, and endocrine-disrupting chemicals (EDCs), pose significant threats to water quality due to their persistence, toxicity, and resistance to conventional treatments. This review is the first to comprehensively evaluate bacterial cellulose (BC), a biodegradable nanofibrillar polysaccharide produced by Komagataeibacter species, as a versatile platform for mitigating these contaminants, addressing a critical gap compared to broader reviews on emerging contaminants or other materials. BC's high surface area, mechanical strength, and tunable chemistry enable adsorption, photodegradation, and biodegradation, achieving 90-98 % removal efficiencies for PFOS, nanoplastics, and EDCs. Functionalization like carboxymethylation, zwitterionic coatings, and composites with metal-organic frameworks (MOFs), TiO₂, or graphene oxide enhance selectivity and capacity through electrostatic attraction, hydrophobic interactions, and π-π stacking. Microbe immobilization on BC facilitates EDC biodegradation, while machine learning-guided designs optimize surface chemistry. Challenges include selectivity in complex wastewater matrices, scalability, high production costs, and regulatory hurdles, addressed through agricultural waste feedstocks, airlift bioreactors, and ISO-compliant testing. This review synthesizes BC's transformative potential, compares its performance to traditional technologies, and proposes a research roadmap integrating hybrid systems and pilot-scale validation for sustainable water treatment.

PMID:41264943 | DOI:10.1016/j.scitotenv.2025.180976


Bacterial cellulose for emerging contaminants: A review of applications for PFAS, nanoplastics, and endocrine disruptors in water treatment - November 20, 2025

Sci Total Environ. 2025 Nov 19;1008:180976. doi: 10.1016/j.scitotenv.2025.180976. Online ahead of print.

ABSTRACT

Emerging contaminants, including per- and polyfluoroalkyl substances (PFAS), nanoplastics, and endocrine-disrupting chemicals (EDCs), pose significant threats to water quality due to their persistence, toxicity, and resistance to conventional treatments. This review is the first to comprehensively evaluate bacterial cellulose (BC), a biodegradable nanofibrillar polysaccharide produced by Komagataeibacter species, as a versatile platform for mitigating these contaminants, addressing a critical gap compared to broader reviews on emerging contaminants or other materials. BC's high surface area, mechanical strength, and tunable chemistry enable adsorption, photodegradation, and biodegradation, achieving 90-98 % removal efficiencies for PFOS, nanoplastics, and EDCs. Functionalization like carboxymethylation, zwitterionic coatings, and composites with metal-organic frameworks (MOFs), TiO₂, or graphene oxide enhance selectivity and capacity through electrostatic attraction, hydrophobic interactions, and π-π stacking. Microbe immobilization on BC facilitates EDC biodegradation, while machine learning-guided designs optimize surface chemistry. Challenges include selectivity in complex wastewater matrices, scalability, high production costs, and regulatory hurdles, addressed through agricultural waste feedstocks, airlift bioreactors, and ISO-compliant testing. This review synthesizes BC's transformative potential, compares its performance to traditional technologies, and proposes a research roadmap integrating hybrid systems and pilot-scale validation for sustainable water treatment.

PMID:41264943 | DOI:10.1016/j.scitotenv.2025.180976


Per- and polyfluoroalkyl substances trigger autoimmune diseases through inflammatory cytokines-IL-17/Th17 signaling axis - November 20, 2025

Chem Biol Interact. 2025 Nov 19;423:111837. doi: 10.1016/j.cbi.2025.111837. Online ahead of print.

ABSTRACT

This study systematically investigates the mechanisms by which per- and polyfluoroalkyl substances (PFAS) promote immune dysregulation and trigger autoimmune diseases (ADs). Using an integrated network toxicology and bioinformatics approach, we identified core molecular interactions between PFAS and five ADs-rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), ankylosing spondylitis (AS), and vasculitis. By combining data from STITCH, SwissTargetPrediction, Comparative Toxicogenomics Database, GeneCards, and OMIM, we identified shared targets linked to both PFAS exposure and AD pathogenesis. Functional enrichment analysis was performed using DAVID, and protein-protein interaction networks were constructed with STRING and visualized in Cytoscape to highlight core targets. Gene expression data from the GEO database revealed the upregulation or downregulation of these targets across these ADs. Molecular docking performed with CB-Dock2 confirmed robust binding between six PFAS and core targets, notably IL1B, TNF, IL6 and ALB. Importantly, we identified a common pathological mechanism involving PFAS-mediated disruption of the inflammatory cytokine axis (IL1B, TNF, IL6) and IL-17/Th17 signaling pathway, which triggers ADs. Furthermore, compared to PFOS, its alternative 6:2 Cl-PFESA showed higher binding affinity to core targets, suggesting greater environmental and health risks that warrant re-evaluation. In conclusion, our research has provided novel and important insights into environmental health and ADs by clarifying core targets and potential mechanisms, and has expanded the evidence into the molecular mechanism of PFAS-induced immunotoxicity and linking PFAS exposure to ADs.

PMID:41265816 | DOI:10.1016/j.cbi.2025.111837


No place to hide: Marine habitat does not determine per- and polyfluoroalkyl substances (PFAS) in odontocetes - November 19, 2025

Sci Total Environ. 2025 Nov 18;1007:180701. doi: 10.1016/j.scitotenv.2025.180701. Online ahead of print.

ABSTRACT

As meso- and apex predators in food webs, marine mammals can bioconcentrate persistent environmental contaminants like per- and polyfluoroalkyl substances (PFAS). Although the presence of PFAS is widely reported in the marine environment, there is a lack of data for cetaceans in Oceania. We investigated whether ecological habitat influences bioconcentration patterns across a range of odontocete (toothed whale, dolphin and porpoise) species. We measured PFAS in liver samples (n = 127) from 16 cetacean species representing four families inhabiting four marine habitats along the Aotearoa New Zealand coastline. We analysed six perfluoroalkyl carboxylic acids, ten perfluoroalkyl sulphonic acids and four precursor compounds in the context of sex, body index, habitat and species/family using generalized linear mixed models. Results showed that marine habitat remained a weak predictor of PFAS burden. Instead, biological factors including sex and age class best explained the levels of PFAS detected across all species and habitats. We offer first important insights on PFAS levels across several new taxa globally, including endemic endangered species and poorly described polar vagrants. Our findings further highlight how the ubiquitous nature of PFAS pose a higher risk to odontocetes across different seascapes than previously anticipated.

PMID:41260118 | DOI:10.1016/j.scitotenv.2025.180701


Multi-dimensional insights into the association between PFOA exposure and NAFLD: An integrative analysis of epidemiology, transcriptomics, and molecular docking - November 19, 2025

Ecotoxicol Environ Saf. 2025 Nov 18;307:119408. doi: 10.1016/j.ecoenv.2025.119408. Online ahead of print.

ABSTRACT

Perfluorooctanoic acid (PFOA), a persistent organic pollutant from the PFAS family, is widely detected in the environment and human blood, raising significant concerns about its long-term health effects. This study explores the potential association between serum PFOA exposure and non-alcoholic fatty liver disease (NAFLD) by integrating data from the NHANES 2003-2012 cohort, global disease burden data (GBD 2021), and toxicogenomic analyses. Weighted logistic regression revealed that individuals in the highest tertile of PFOA exposure had a significantly increased risk of NAFLD (adjusted OR = 1.45, 95 % CI: 1.01-2.07). Restricted cubic spline analysis further supported a nonlinear dose-response relationship. Transcriptomic analysis identified five hub genes (IL6, IL1B, FOS, MYC, CDKN1A) potentially involved in lipid metabolism, inflammation, and cell cycle regulation. Molecular docking suggested high binding energy between PFOA and the encoded proteins, indicating possible interference with key hepatic functions. Together, these findings offer preliminary insights into potential mechanisms by which environmentally relevant levels of PFOA might be involved in NAFLD development. This integrative approach serves as a hypothesis-generating framework for future studies on biomarker discovery, risk assessment, and environmental health policy.

PMID:41260040 | DOI:10.1016/j.ecoenv.2025.119408


Environmental behavior and human health risks of PFAS: occurrence, toxicity, and the state-of-the-art removal approaches - November 19, 2025

RSC Adv. 2025 Nov 17;15(52):44555-44583. doi: 10.1039/d5ra07672b. eCollection 2025 Nov 11.

ABSTRACT

Fluorinated compounds, including poly- and per-fluoroalkyl substances (PFAS), are characterized by complex behavior, environmental persistence, and resistance to degradation. These thermally stable compounds repel both oil and water. Concerns are mounting over their bioaccumulation in humans and other organisms, given their associated health risks such as endocrine disruption, immune suppression, obesity, elevated cholesterol levels, and cancer. Low concentrations of PFAS detected in drinking water present a potential human exposure pathway. This review addresses the occurrence and exposure pathways of PFAS; their toxicity in humans, plants, and animals; analytical methods for their detection and quantification in aqueous matrices; and their removal techniques including membrane technologies, advanced oxidation processes, adsorption, ion exchange, biological methods, and hydrothermal liquefaction. The factors affecting the removal of PFAS, such as inorganic anions and cations, natural organic matter, and other organic pollutants in wastewater, are also included. Additionally, cost-effective and environmentally friendly methods for regenerating adsorbents are explored. The conclusion discusses the current restrictions and future perspectives on the analysis of PFAS.

PMID:41255867 | PMC:PMC12621309 | DOI:10.1039/d5ra07672b


Environmental behavior and human health risks of PFAS: occurrence, toxicity, and the state-of-the-art removal approaches - November 19, 2025

RSC Adv. 2025 Nov 17;15(52):44555-44583. doi: 10.1039/d5ra07672b. eCollection 2025 Nov 11.

ABSTRACT

Fluorinated compounds, including poly- and per-fluoroalkyl substances (PFAS), are characterized by complex behavior, environmental persistence, and resistance to degradation. These thermally stable compounds repel both oil and water. Concerns are mounting over their bioaccumulation in humans and other organisms, given their associated health risks such as endocrine disruption, immune suppression, obesity, elevated cholesterol levels, and cancer. Low concentrations of PFAS detected in drinking water present a potential human exposure pathway. This review addresses the occurrence and exposure pathways of PFAS; their toxicity in humans, plants, and animals; analytical methods for their detection and quantification in aqueous matrices; and their removal techniques including membrane technologies, advanced oxidation processes, adsorption, ion exchange, biological methods, and hydrothermal liquefaction. The factors affecting the removal of PFAS, such as inorganic anions and cations, natural organic matter, and other organic pollutants in wastewater, are also included. Additionally, cost-effective and environmentally friendly methods for regenerating adsorbents are explored. The conclusion discusses the current restrictions and future perspectives on the analysis of PFAS.

PMID:41255867 | PMC:PMC12621309 | DOI:10.1039/d5ra07672b


Identification and quantification of per- and polyfluoroalkyl substances in wastewater from Taiwan using targeted and non-targeted approaches - November 19, 2025

Chemosphere. 2025 Nov 18;393:144762. doi: 10.1016/j.chemosphere.2025.144762. Online ahead of print.

ABSTRACT

This study assessed per- and polyfluoroalkyl substances (PFAS) in municipal wastewater influents in Taiwan using a high-resolution mass spectrometry (HRMS) workflow combining targeted and non-targeted analyses. Targeted analysis detected seven PFAS above quantification, with perfluorooctane sulfonate (PFOS, 5.33-8.37 ng/L) at the highest levels, followed by PFHxS (1.31-2.88 ng/L), PFBS (0.88-1.26 ng/L), and 6:2 fluorotelomer sulfonate (up to 3.40 ng/L). Short-chain acids such as PFBA and PFPeA were mostly below quantification. Non-targeted screening expanded the PFAS inventory to 45 compounds, including ultra-short-chain PFAS (e.g., trifluoroacetic acid, trifluoromethanesulfonic acid) and multiple precursors. The diversity of detected PFAS underscores the importance of integrating non-targeted strategies into wastewater monitoring. These findings provide the first nationwide PFAS profile for Taiwanese municipal wastewater and establish a baseline for future environmental surveillance and regulatory development.

PMID:41260055 | DOI:10.1016/j.chemosphere.2025.144762


Amphipathic fluoroamine-functionalized hydrogels for enhanced selective removal of anionic pfas from water - November 19, 2025

Nat Commun. 2025 Nov 19;16(1):10152. doi: 10.1038/s41467-025-65031-4.

ABSTRACT

Effective treatment of per- and polyfluoroalkyl substances (PFAS) in an affordable manner is highly demanded to meet stringent water protection standards. Herein, we introduce a fluoroamine dual-site hydrogel (QFgel) designed to structurally match amphipathic PFAS molecules, facilitating selective interactions for the effective PFAS removal from water. Specifically, the synergistic effects of quaternized and fluorinated functional groups in QFgel can promote electrostatic-fluorophilic dual-site interactions with both the perfluoroalkyl and anionic headgroups at the ends of PFAS. As a result, these dual-site interactions achieve high selectivity (sorption coefficients ranging from 1.75 to 4.0) and ultrahigh sorption capacity (up to 2,835 mg g-1), resulting in over 95.6% removal of 17 PFAS types at environmentally relevant concentrations in real water matrices. Notably, pilot-scale applications with a kilogram-scale QFgel-adsorber effectively treats up to 12,400 and 9,215 bed volumes of PFAS-contaminated drinking water (i.e., tap water) before the breakthrough point of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) ([PFAS]0 = ~ 0.35 µg L-1, 2 m3 per day). After 46 days of continuous operation, the adsorber is regenerated using a saline-methanol mixed eluent, achieving 96.5% desorption and up to 1,633-fold PFAS enrichment, while reducing eluent use by 70% compared to commercial sorbents. This work advances PFAS remediation by offering a scalable, cost-effective solution, and contributes to sustainable water resource protection.

PMID:41258127 | PMC:PMC12630723 | DOI:10.1038/s41467-025-65031-4


A comparative toxicological and epidemiological evaluation of dioxins and PFAS chemicals - November 19, 2025

Crit Rev Toxicol. 2025 Nov 19:1-58. doi: 10.1080/10408444.2025.2560827. Online ahead of print.

ABSTRACT

Regulatory frameworks, informed by robust and transparent scientific evidence, can significantly benefit society when thoughtful and measured regulation is promulgated. However, regulations founded on incomplete or misinterpreted science often result in unintended consequences. As was the case with the polychlorinated dibenzodioxin and polychlorinated dibenzofuran (PCDD/PCDF) chemicals, for the past 50 years, there has been a lack of scientific consensus on the adverse health effects of per- and polyfluoroalkyl substances (PFAS) in humans at current blood concentrations (about 4 ppb TEQ) or even concentrations 10-300-fold higher (40-1200 ppb TEQ). Despite their distinctly different chemical structures, the dioxins, particularly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and perfluorooctanoic acid (PFOA)/perfluorooctanesulfonic acid (PFOS), share notable similarities: environmental persistence, biological recalcitrance, slightly unpredictable acute toxicity, a lack of genotoxicity, and suggestive data on adverse health effects in humans; across a wide range of doses. Both substances display varying degrees of acute toxicity across species, and both have been associated with the onset of wasting syndrome in certain animals at fairly high doses, but wasting syndrome is not seen in humans. Although there is moderate to high acute toxicity in multiple animal species for both families of chemicals, there is low acute toxicity in humans. In humans, both compounds interact with fatty acid metabolism. The evidence indicates that both are either weakly genotoxic or non-genotoxic. The dioxins can cause cancer in a variety of animal species, but even in humans exposed to high doses, no increased cancer risk is apparent. PFAS chemicals are similar; weakly carcinogenic in animals and, perhaps, lacking carcinogenic potency in humans. However, unlike with dioxins, high human exposure to PFAS has only occurred in the workplace; thus, few data from highly exposed human populations are available to rigorously evaluate the human cancer risk or other potential effects at elevated doses. Similar to the widespread presence of dioxins reported in the 1970s-1980s, PFAS chemicals are now globally ubiquitous, with detectable concentrations in nearly every individual, fish, and wildlife species. As awareness has increased over time, pressure to prevent the release or manufacture of PFOA and PFOS has decreased the blood concentrations in Americans by 10-fold over the past 15 years, paralleling trends observed with the dioxins when global concerns surfaced. The dioxins were regulated in a heavy-handed manner despite scientific uncertainty regarding their human health risks over a range of exposure levels, as well as a lack of consensus on dose-response relationships, thresholds for adverse effects, and human relevance of high-dose animal studies. The regulatory actions that occurred with the dioxins ultimately resulted in substantial economic and societal costs, even in the face of much uncertainty. This paper examines the parallels between the development of scientific understanding of the health hazards and the eventual regulation of dioxins and PFAS chemicals. For both families of chemicals, the precautionary principle was followed by most agencies rather than solid scientific data during the rulemaking process.

PMID:41257450 | DOI:10.1080/10408444.2025.2560827


Electrochemical degradation of PFOA using unmodified graphite electrodes: a scalable approach for PFAS remediation - November 19, 2025

Environ Sci Pollut Res Int. 2025 Nov 19. doi: 10.1007/s11356-025-37054-3. Online ahead of print.

ABSTRACT

Perfluorooctanoic acid (PFOA) is a category of PFAS (per- and polyfluoroalkyl substances), particularly prevalent in aquatic environments, and this study investigated the effectiveness of electrochemical oxidation using cost-effective graphite electrodes for PFOA degradation with sodium sulfate as the supporting electrolyte. Optimization studies revealed maximum degradation efficiency at pH 3, 45 mA/cm2 current density, 20 mM electrolyte concentration, and 4-h treatment time. Under these conditions, the system achieved 85% total organic carbon (TOC) removal, 84.19% PFOA degradation confirmed by high-resolution mass spectrometry, and defluorination, demonstrating substantial mineralization of PFOA. High-resolution mass spectrometry identified a degradation pathway proceeding through defluorination, decarboxylation, hydroxylation, and dehydroxylation mechanisms, with heptafluoropropane identified as the final organic intermediate before complete mineralization to CO₂, H₂O, and fluoride ions. The system followed a decarboxylation-hydroxylation-elimination-hydrolysis (DHEH) mechanism. Ion chromatography confirmed significant defluorination, with fluoride concentrations increasing from 13.1 to 884.33 μg/L. Characterization of electrodes revealed surface modifications that enhanced electrochemical activity while maintaining structural integrity. These findings demonstrate that graphite electrodes offer a cost-effective alternative to expensive boron-doped diamond electrodes for PFOA removal while maintaining comparable performance.

PMID:41258284 | DOI:10.1007/s11356-025-37054-3


Machine Learning Modeling of Zebrafish Toxicity Endpoints After Exposure to PROTACs - November 19, 2025

Toxicol Sci. 2025 Nov 19:kfaf162. doi: 10.1093/toxsci/kfaf162. Online ahead of print.

ABSTRACT

Zebrafish (danio rerio) are an ideal system for understanding developmental toxicity as they display similar toxicity outcomes to other vertebrates. Further, many molecules have been tested for developmental toxicity in zebrafish providing an opportunity for machine learning model development. We curated 1345 small molecules from ToxCast, flame retardant compounds, per- and polyfluoroalkyl substances (PFAS), and industrial chemicals published by the Superfund Research Program (SRP). Following curation, we trained machine learning models on the zebrafish toxicity endpoints ANY_ = any effect including mortality, ANY_BUT_MORT = any effect excluding mortality, MORT = mortality ie did the embryo die, EDEM = did an edema form, CRAN = Craniofacial malformation. We demonstrated that these models were better than random when compared to shuffled data. We also fine-tuned the molecular SMILES encoder MolBART to predict on all zebrafish toxicity endpoints and found it generally matched the performance of classical machine learning models for ANY_BUT_MORT, CRAN, and EDEM endpoints. We present new toxicity data for Proteolysis Targeting Chimeras (PROTACs) in Zebrafish and machine learning models for these data by fingerprinting different parts of the molecule individually, yielding predictive performance (AUROC 0.6-0.7). If we are to reduce animal testing with new approach methodologies (NAMs) like these Zebrafish toxicity models they need to be able adapt to new molecular classes like PROTACs.

PMID:41259055 | DOI:10.1093/toxsci/kfaf162


Per- and polyfluoroalkyl substances (PFAS) in fish collected from the Rio Grande and reservoirs in northern New Mexico - November 19, 2025

PLoS One. 2025 Nov 19;20(11):e0336856. doi: 10.1371/journal.pone.0336856. eCollection 2025.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are a group of industrial and commercial chemicals widely used throughout the world due to their beneficial chemical properties. Because of their widespread use, their chemical stability, and their ability to be transported over long distances through atmospheric deposition and movement through waterways, PFAS are found throughout most aquatic ecosystems; yet large sampling gaps exist among reservoir and river ecosystems in the desert southwest of the United States. In this study, we examine PFAS concentrations in the tissue of fish (catfish [channel and blue], common carp, smallmouth bass, northern pike, walleye, white crappie and white sucker) collected in northern New Mexico, including examining PFAS composition and concentration relative to trophic level distribution. We collected fish from two man-made reservoirs and from the Rio Grande. We then collected muscle and liver tissues from fish specimens, which were screened for 39 PFAS compounds. We detected PFAS compounds in most fish tissue sampled, including the biomagnification of PFAS compounds within liver samples, with PFOS concentrations ranged from 1.13 to 350.1 (64.4 average) times higher in the liver samples compared to muscle samples. Most PFAS concentrations within muscle samples were within the range of atmospheric transportation previously reported and average tissue concentrations of PFAS were calculated to be 2.02 ± 1.81 ng g-1. Using stable isotopes as a predictor of trophic-foraging exposure and PFAS concentrations, we noted a correlation between enriched δ15N values, which had higher perfluorodecanoic acid concentrations.

PMID:41259316 | PMC:PMC12629422 | DOI:10.1371/journal.pone.0336856


Environmental Occurrence, Source Identification, and Health Hazards of Ultrashort-Chain PFAS in the Yangtze River Delta - November 19, 2025

Environ Sci Technol. 2025 Nov 19. doi: 10.1021/acs.est.5c09274. Online ahead of print.

ABSTRACT

Ultrashort-chain per- and polyfluoroalkyl substances (USC-PFAS), defined by three or fewer carbon atoms in their backbone, represent an emerging class of environmental contaminants whose prevalence and hazards remain inadequately characterized. This study conducted a comprehensive survey of seven USC-PFAS and 37 other PFAS compounds in aquatic environments within the Integrated Demonstration Zone of the Yangtze River Delta, a region undergoing continued industrialization. Results showed that USC-PFAS overwhelmingly dominated PFAS profiles, with trifluoroacetic acid (TFA) representing the most abundant species. Mean concentrations of TFA reached 8.7 × 104 ng/L in surface water, 8.0 × 104 ng/L in source water, and 6.9 × 104 ng/L in tap water, constituting 90.1% to 99.6% of total ∑44PFAS across matrices. When TFA was excluded, the remaining ∑6USC-PFAS contributed 44.0% to 58.8% of the total PFAS burden. Trifluoromethanesulfonic acid (TFMS) was the second most abundant in surface and source waters, while trifluoromethane sulfonimide (Ntf2) ranked second in tap water. Source apportionment analyses implicated battery electrolyte formulations as major contributors of TFMS and Ntf2. Hazard prioritization based on persistence, mobility, bioaccumulation, and toxicity (PMBT) metrics, alongside measured environmental levels, identified TFA, TFMS, perfluoro-2-(perfluoromethoxy)propanoic acid (PMPA), and perfluorooctanoic acid (PFOA) as high-hazard compounds. These findings suggest that USC-PFAS constitute a pervasive and underregulated class of pollutants, whose high mobility and recalcitrance challenge current assumptions regarding their environmental safety and call for urgent regulatory reevaluation.

PMID:41259719 | DOI:10.1021/acs.est.5c09274


Machine Learning Modeling of Zebrafish Toxicity Endpoints After Exposure to PROTACs - November 19, 2025

Abstract
Zebrafish (danio rerio) are an ideal system for understanding developmental toxicity as they display similar toxicity outcomes to other vertebrates. Further, many molecules have been tested for developmental toxicity in zebrafish providing an opportunity for machine learning model development. We curated 1345 small molecules from ToxCast, flame retardant compounds, per- and polyfluoroalkyl substances (PFAS), and industrial chemicals published by the Superfund Research Program (SRP). Following curation, we trained machine learning models on the zebrafish toxicity endpoints ANY_ = any effect including mortality, ANY_BUT_MORT = any effect excluding mortality, MORT = mortality ie did the embryo die, EDEM = did an edema form, CRAN = Craniofacial malformation. We demonstrated that these models were better than random when compared to shuffled data. We also fine-tuned the molecular SMILES encoder MolBART to predict on all zebrafish toxicity endpoints and found it generally matched the performance of classical machine learning models for ANY_BUT_MORT, CRAN, and EDEM endpoints. We present new toxicity data for Proteolysis Targeting Chimeras (PROTACs) in Zebrafish and machine learning models for these data by fingerprinting different parts of the molecule individually, yielding predictive performance (AUROC 0.6-0.7). If we are to reduce animal testing with new approach methodologies (NAMs) like these Zebrafish toxicity models they need to be able adapt to new molecular classes like PROTACs.